Neuro Flashcards
Epi/ Grading of pilocytic astrocytoma
Benign tumours; Grade I (WHO)
* Children and young adults
Location of Pilocytic astrocytoma
* Cerebellum (most common)
* Third ventricle
* Optic pathways
* Spinal cord
* Cerebral hemispheres
Macroscopic Features: ‘
* Cystic lesion with a mural nodule in the wall of the cyst or
* Solid, well circumscribed mass
Microscopic Findings:
* Bipolar cells with long, thin hair-like processes
* Rosenthal fibers
* Eosinophilic granular bodies
* Microcystic changes
features of ?
Pilocytic astrocytoma (WHO GRADE 1)
Epi of Diffuse Astrocytomas
80% of adult gliomas
loc of Diffuse astrocytomas
Cerebral hemispheres
Classification of Diffuse astrocytomas
1) Well-differentiated astrocytoma (WHO Grade II)
2) Anaplastic astrocytoma (WHO Grade III)
3) Glioblastoma (WHO Grade IV)
Gentic predisposition of Diffuse Astrocytomas
1) Loss of function mutations in p53 and Rb genes (Glioblastomas)
2) Mutations in the IDH1and IDH2 genes (Low grade astrocytomas) –> Important diagnostic utility
Macro features:
* Gray, poorly defined, infiltrative tumours
Microscopic features:
* Mild to moderate hypercellularity
* Variable nuclear pleomorphism
* Fibrillary appearance Fine (GFAP [+]) astrocytic cell processes
* Irregular and Hyper-chromatic “Naked nuclei”
features of?
Well-differentiated astrocytoma -WHO Grade II
Macro features:
* Firm and white
* Soft and yellow
* Cystic degeneration and haemorrhage
Micro features:
* “Glomeruloid” bodies: Larger tufts of microvascular hyperplasia with multiple lumens
* Marked cellularity
* Pseudo-palisading necrosis
features of?
Glioblastoma (WHO Grade IV)
Macroscopic Features:
* Gelatinous, gray masses, possible with cysts, focal haemorrhage and calcification
Microscopic features:
* Sheets of sphaerical cells with spherical nuclei
* Finely granular chromatin
* Perinuclear halo (“fried egg appearance”)
* Delicate network of anastomosing capillaries (“chicken-wire appearance”)
* Focal or diffuse deposits of calcification
features of?
Well- Differentiated Oligodendroglioma
Loc of Epyndymoma
- Children and adolescents –> Near 4th ventricle
- Adults –> Spinal cord
Macroscopic Features:
* Solid or papillary masses (originating from the ventricular floor)
Microscopic Findings:
* Cells with regular round to oval nuclei
* Abundant granular chromatin
* Dense fibrillary background
* True rosettes (around a lumen)
* Perivascular pseudo-rosettes
featues of?
Conventional Ependymoma (WHO GRADE II)
- Increased cell density, nuclear pleomorphism, high mitotic index, necrosis (Anaplastic Ependymomas)
3 Examples of neuronal Tumours
1) Central Neurocytoma (low-grade)
2) Gangliogliomas (low-grade astrocytoma)
3) Dysembryoplastic Neuroepithelial Tumour (low-grade childhood tumour)
loc of Central Neurocytoma
lateral or 3rd ventricles
Microscopic Findings:
* Evenly spaced, round, uniform nuclei
* Often islands of neuropil
* Densely packed small- to medium- sized, round bland tumour cells
features of ?
Central neurocytoma
CM of Gangliogliomas
Seizures
loc of Dysembryoplastic neuroepithelial tumour (DNT)
Superficial temporal lobe
Microscopic Findings:
* Small round neuronal cells arranged in columns and around central cores of processes
* Intra-cortical nodules with myxoid background
* “Floating neurons” within a myxoid fluid (Mucin-filled cyst)
features of?
Dysembryoplastic Neuroepithelial Tumour (DNT)
CM of Dysembryoplastic Nuro-Epithelial tumour (DNT)
Seizures
Embryonal (Primitive) Neoplasms are known to have what distinctive appearance ?
Primitive “small round cell” appearance –> Resemblance to normal progenitor cells of CNS
Macroscopic Features:
* Well circumscribed, gray and friable
* Extension to the leptomeninges
Microscopic Findings:
* Extremely cellular tumours
* Sheets of anaplastic (“small blue”) cells
* Hyperchromatic nuclei
* Mitoses
* Focal neuronal differentiation with Homer-Wright rosettes
featurs of?
Medulloblastoma
Loc of Medulloblastoma
- Midline of the cerebellum (children);
- Lateral cerebellar tumours (adults)
who is as high risk of developing primary CNS Lymphomas
immune-compromised individuals <> EBV [+]
Macroscopic Features:
* Multiple nodules within the brain parenchyma
* Well defined tumours
* Necroses (EBV[+] tumours)
* Localisation: Deep gray structures, white matter and cortex
Microscopic Findings:
* Diffuse Large B-Cell Lymphomas (DLBCL)
* Perivascular accumulation of neoplastic cells
* Infiltration of the adjacent brain parenchyma
features of?
Primary CNS lymphoma
Most common CNS germ cell neoplasm ?
Germinoma (resemblance to testicular Seminoma)
* seminoma -> lymphocytic infiltrates
Loc of Germ Cell tumours
i. Pineal, ii. Supra-sellar regions
Loc of Meningioma
- Anywhere on the external surfaces of the brain (meninges)
- Within the ventricular system
Micro findings:
* Sheets or clusters of cells without visible cell membranes
* Large nests of epithelioid cells
* Numerous nuclear clear holes
Features of what type of Grade I Meningioma?
Meningotheliomatous (Synctial)
Micro features:
* Elongated cells with abundant collagen deposits between them
* Intersecting fascicles of spindled cells
features of what type of Grade I Meningioma?
Fibroblastic Meningioma
Micro features:
* Combined features of syncytial and fibroblastic tumours
* Psamoma bodies
* characteristic “Whorls”
fetaures of what type of Grade I Meningioma?
Transitional Meningioma
micro features:
* Presence of numerous psammoma bodies
features of what type of Grade I Meningioma?
Psammomatous Meningioma
Micro features:
* Presence of pseudo-psammoma bodies (PAS [+] eosinophilic secretions)
* Tan Appearance on cut surface
features of what type of Grade I Menongioma?
Secretory Meningioma
What stain is used for the identification eosinophilic pseudo-psammoma bodies in Secretory Meningioma ?
PAS ([+])
Macroscopic features:
* soft fleshy appearance with papillary (cauliflower-like) configuration
Microscopic features:
* Prominant nucleoli
* Focus of “spontaneous necrosis”
* MIB-1 (Ki-67 > 4%)
features of?
Atypical Meningioma (WHO GRADE II)
Macroscopic features:
* Tumour with irregular contour and inhomogeneous signal characteristics
* Central hypodensity (suggestive of necrosis)
* Tumour with soft, almost gelatinous cut surface (suggestive of high cellularity)
Microscopic featuers:
* Fibrosarcoma-like spindled region
* Carcinoma-like region ; Multiple necrosis
* patchy postitivity to EMA (stain)
* MIB-1 (Ki-67) > 20%
features of?
Anaplastic Meningioma (WHO Grarde III)
Microscopic features:
* Tongue-like protrusions
* Entrapped brain parenchyma [GFAP]
features of?
Brain invasive meningioma (WHO GRADE II)
* GFAB stains the glial cells in the brain parenchyma
Macroscopic Features:
* Sharply demarcated masses with peri-tumoural oedema
Microscopic features:
* Tall columnar cells
* Cribriform glands
* “Dirty necrosis”
features of?
Metastaic barin tumour from the GI tract (Colon Carcinoma)
A mononeuropathy Syndrom
* peripheral nerve injury (single nerve)
Carpal Tunnel Syndrom
(compression of the median nerve)
cause of Gullain-Barre Syndrome
* Rapidly progressive acute demyelinating disorder
1) Infection (e.g. CMV, EBV, HIV, etc.) or vaccine –> Break down of self-tolerance –> Autoimmune response
2) Involvement of both humoral and cellular immune responses
Epi of Schwannomas (Neurilemmomas)
- bening
- Sporadic (most common); 10% associated with familial NF2
loc of Schwannomas
- Soft tissues
- Internal organs
- Spinal nerve roots
- Cranial nerves (Vestibular portion of the 8th nerve
Macroscopic Features:
* Circumscribed masses next to a nerve
* Globualr enlargment of a fascicle
* Yellow colouration of the cut surface, due to lipid accumulation
Microscopic Findings:
* Alternating areas of dense (“Antoni A”) and loose (“Antoni B”) texture
* **“Antoni A” **areas: Bland spindle cells arranged into intersecting fascicles
* “Verocay bodies”: Structures composed of alternating bands of nuclear palisading and anuclear strands between them
* Thick-walled hyalinised vessels
* Possible, presence of haemorrhage or cystic changes
features of?
Shwannomas (Neurilemmomas)
caues of Neurofibromatois Type 2
Loss of function mutation of the NF2 gene affecting Merlin (Schwannomin) protein
CF of NF2
Bilateral vestibular Schwannomas -> Hallmark of Neurofibromatosis Type 2
Hallmark of Neurofibromatosis Type 2?
Bilateral vestibular Schwannomas
Microscopic Findings:
* Non-encapsulated tumours
* Haphazard cellular growth pattern
* Admixture of Schwann cells w wavy nuclei, mast cells, fibroblast-like cells and perineurial-like cells
* Background stroma: Loose wavy or dense collagen bundles or even myxoid consistency
features of?
Neurofibromatosis Type 2
localized Cutaneous Neurofibromas can exist as?
- solitary lesions or multiple in the context of NF1
- Superficial nodular or polypoid masses
Pathogonomic (symptom/sign) of NF1
Plexiform Neurofibromas
Microscopic Findings:
* Presence of residual axons found among the neoplastic cells
* Proliferation of schwann cells and fibroblasts
* Enlargement of the nerve
* Intact perineurium
* Classic “bag of worms appearance”
features of?
Plexifrom Neurofibromas
Diffuse Neurofibromas are ass w/?
NF1
Microscopic findings:
* Extensive infiltration of the dermis and subcutis
* Subcuataneous masses
* Marked expansion of dermal tissue
features of?
Diffuse Neurofibromas
Neurofibromatosis Type 1 is AKA?
Von Recklinghausen disease
who is likely to develop Malignant Peripheral Nerve Sheath tumours?
NF1 px
Cause of Conjuctivitis
Adenovirus (most common), bacteria
CM of Retinitis Pigmentosa
1) Retinal pigmentation
2) Peripheral vision loss (“Tunnel vision”) and progressive loss of Central Vision
patho of Senile Macular Degenration
Loss of central vision and pigmentary changes or haemorrhage in the macula
patho/CM of Angle-Closure Galucoma
Angle-Closure Glaucoma:
* Narrow anterior chamber angle
* Increase in intraocular pressure on dilatation of pupil
symptoms of open angle Glaucoma
1) Gradual loss of peripheral (side to side & up/down) visions, usually in both eyes
2) Tunnel vission
Explain the “two hit” hypothesis of tumour development in Retinoblastoma
1) First “hit”: Inherited deletion in germ cells (familial cases) or somatic mutation (sporadic cases)
2) Second “hit”: Somatic mutation (both familial and sporadic cases)
Signs of Retinoblastoma
1) swollen eyes
2) shrunken eyes
3) A red, sore or swollen eye w/o infection
4) A white refelction in the pupil
Microscopic features:
- Multiple foci of necrosis
- Numerous apoptotic cells
- True rosette
- scant cytoplasm
- Flexner-Wintersteiner rosette
- Round to oval nuceli and finely granualr chromattin
features of?
Retinoblastoma
what are the 2 types of cerebral odema
1) Vasogenic oedema
2) Cytotoxic oedema
Macroscopic Features:
- Flattening of the gyri and narrowing of the intervening sulci
- Compression of the ventricular cavities
features of?
Cerebral Oedema
What are the 3 types of Herniation syndromes
1) Subfalcine (Cingulate) herniation under Falx cerebri
2) Uncal Transtentorial herniation <>Tentorium cerebelli
3) Cerbellar tonsillar herniation into the Foramen magnum
What are the 3 sites of brain herniation?
1) Falx cerebri –> (Subfalcine (Cingulate) herniation)
2) tentorium cerebelli -> (transtentorial [Uncinate] hernia)
3) Foramen magnum –> Tonsillar hernia)
Compression of which artery is caused by Subfalcine (Cingulate) Herniation ?
anterior cerebral artery
microscopic features:
- Cortical spongious alteration
- Peri-neuronal/ Peri-vascualar swelling of astrocytic processes
features of?
Cytotoxic Cerebal Oedema
Compression ————- nerve in a Transitional (Ucinate) Hernitation –> Pupilary dilatation
Third cranial nerve
In a Transtenotorial (Uncinate) Herniation , the compression of ———– –> Kernohan’s notch
Contralateral cerebral peduncle against the tentorium
In a Transtentorial (Uncinate) Herniation, the compression of ———– -> Ischaemic injury of the primary visual cortex
Posterior cerebral artery
The 2 mechanisms that deprive O2 from the brain
1) Functional Hypoxia
2) Ischaemia due to tissue Hypoperfusion
cause of Global Cerebral Ischaemia
Severe systemic hypotension (as in cardiac arrest or shock)
Macroscopic Features of Global Cerebral Ischaemia:
* ————-, with ————— and narrowed sulci
* Poor demarcation between gray and white matter
Swollen brain, with widened gyri and narrowed sulci
What neuronal cells are affected by Global cerebral Ischaemia
- Pyramidal cells of hippocampus and neocortex
- Purkinje cells of the cerebellum
Immunohistochemistry used to stain Astrocytes
GFAP
Marker used for microglia staining
* microglia –> macrophages of the brain
CD68
* stains macropahges
cause of “Watershed infarcts”
Hypotensive episodes
(Anaphylactic shock, sudden blood loss, sever infections)
location of “Watershed infarcts”
The border-zone between the anterior and middle cerebral artery distributions
CF of “watershed” infarcts
1) Transient post-ischaemic confusional state –> Complete recovery (mild insult)
2) Sever global cerebral ischaemia–> Widespread neuronal death; Severely neurologically impaired and in a persistent vegetetative state
Most common site of embolic infarction
Middle Cerebral Artery (MCA)
locations of thrombotic occlusions
Carotid bifurcation (,origin of middle cerebral artery)
*carotid bifurcation is the point where the common carotid artery divides into internal and external carotid arteries
The 2 types of infarcts
1) Non-haemorrhagic (Result of acute vascular occlusions)
2) Haemorrhagic (Result of reperfusion of ischaemic tissue, either through collaterals or dissolution of emboli)
*reperfusion->restortion of blood flow to a tissue that has been blocked
Macroscopic Features:
Blood extravasation -> Compression of the neighbouring brain parenchyma –> Cavity formation with brown discoloured rim
Microscopic Findings -Early findings:
* Extra-vasated, clotted blood
* Anoxic neural changes of the adjacent neuropil
* Oedema of the brain parenchyma, around the haemorrhagic focus
features of?
* Anoxic: complete loss of O2 supply
Primary brain Parenchymal Haemorrhage (Early findings)
Late Microscopic findings of Primary brain parenchymal haemorrhage:
* Pigment and ——————–
* ——————— at the periphery of the lesion
- Pigment and lipid-laden macrophages
- Reactive astrogliosis at the periphery of the lesion
Histochemical stain for Beta Amyloid (in Cerebral Amyloid Angiopathy)
Apple-green birefringence on Congo-red
stain used for Haemosiderin (in Cerebral Amyloid Angiopathy)
Pearl’s/Prassin blue iron staining
Pathologocial identifcation of cerebral Amyloid Angiopathy
1) Aβ immuno stain/ Congo red stain for Beta Amyloid
2) Pearl’s blue iron stain for Haemosiderin
causes of Subarrachnoid haemorrahge & Saccular aneurysms
- Rupture of a berry aneurysm (most common)
- Vascular malformation
- Trauma
- Rupture of an intra-cerebral haemorrhage into the ventricular system
- Tumours
loactions of Subarachnoid haemorrhage & Saccular Aneurysms
~90% of Berry aneurysms in the anterior circulation
Microscopic Findings:
* Absent muscle wall and intimal elastic lamina (thinning of vessels)
* Presence of a thickened hyalinised intima, and the adventitia
features of?
Subarachnoid haemorrhage & saccular aneurysms
CF of Subarachnoid haemorrhage & saccular aneurysms
- Sudden, severe headache
- Rapid loss of consciousness
- Death (from the first bleed in 25-50% of cases)
- blood in CSF
- Postive Kernig & Burdzinski sign
the 4 types of Vascular Malformations
1) Arterio-Venous Malformations (AVMs)
2) Cavernous Malformations
3) Capillary Telangiectasias
4) Venous Angiomas
Epi of AVMs (Anter-venous mal.)
Most common vascular malformation
* M:F = 2:1; Age: 10-30 years
Macroscopic Features:
* Tangled network of worm-like vascular channels
Microscopic Findings:
* Enlarged blood vessels, separated by gliotic tissue (shown w/ GFAP)
* Presence of haemo-siderophages
features of?
AVMs (Arterio-venous malformations)
loc of Cavernous Malformations
Cerebellum, Pons
Microscopic Findings:
* Distended, loosely organised vascular channels (Back to back dilated vesseles- Trichome stain)
* Collagenised walls
* No intervening nervous tissue
* Foci of old haemorrhage, infarction and calcification
features of?
Cavernous (Vascular) Malformation
Micro:
* Dilated thin-walled vascular channels
* Intervening normal brain parenchyma
* several large, thin-walled vascualr spaces
* “Pencil fibers” = white matter tracts of the basal ganglia
features of?
Capillary Telangicetasias
Micro:
* Aggregates of ectatic venous channels
* Capillary Hindus resembles the head of medusa
features of?
Venous Angiomas (Varcies)
Microscopic Findings:
* Chronic inflammatory cell infiltrates
* Multinucleate giant cells (+/- granuloma formation)
* Destruction of vessel walls
* Amyloid-β deposits
* Lumen Oblitertion
features of?
Primary Angiitis of the CNS
* Form fo Vasculitis
Contusion Will cause?
haemorrhage, tissue damage and oedema in the brain
Loc of a Contusion
1) Orbito-frontal regions
2) Temporal lobe tips
the 2 types of Contusion
Coup and Contre-Coup injuries
Macroscopic Features:
* Cross-section: Wedge-shaped
* Old lesions: Depressed, yellowish-brown patches (Crests of gyri)
Microscopic Findings:
* Involvement of superficial layer
* Neuronal cell body injury (nuclear pyknosis and cytoplasmic eosinophilia) within 24 hours
* Inflammatory response: Initially neutrophils and later also macrophages
* Old lesions: Gliosis and haemo-siderophages
features of?
Contusion
location of Diffuse Axonal injury (DAI)
- Near the angles of the lateral ventricles
- Corpus callosum
- Brain-Stem
Microscopic Findings:
* Axonal swellings (“bulbs”), within hours of the injury
* Axonal Spheroids
* Immuno-histochemistry : β-APP
features of?
Diffuse Axonal injury
Histochemical stain for diffuse Axonal Injury ?
Silver stain
(detects axonal swelling)
Immuno-Histochemistry findings in Diffuse Axonal Injury
Amyloid Precussor ProteinAPP
Cause of Epidural Haematoma
Traumatic injury of the middle meningeal artery, after a skull fracture
causes of Subdural Haematoma
Tear of the bridging veins, after trauma
location of Subdural Haematoma
lateral aspects of the cerebral hemispheres
Macroscopic Features:
* Collection of freshly clotted blood, over the brain convexity
* Flattening of the underlying brain
* Ruprture of Bridging veins
* star-like invasion of Collagen fibers
* Immuno-histo: Combined leukocyes-macrophage rxn, Siderophages
features of ?
Subdural Haematoma
?? not sure if we need to know this
stain for Siderophages
Prussian-blue reaction
?? not sure if we need know this
Stain used for Erythrophagocytosis
Azan
Progression of Subdural Haematoma
- ——— of the clot (~1 week)
- Development of ————– from dura (2 weeks)
- ——– (1-3 months)
- ———- of the fibrosing lesion -> Thin layer of connective tissue (————”)
- Commonly, ————– (chronic subdural haematoma)
- Lysis of the clot (~1 week)
- Development of Granulation tissue from dura (2 weeks)
- Fibrosis (1-3 months)
- Retraction of the fibrosing lesion -> Thin layer of connective tissue (“Subdural membrane”)
- Commonly, re-bleeding (chronic subdural haematoma)
Which condition is known as “Smooth brain” ?
Lissencephaly
patho of Lissencephaly
Total absence of gyration or pachygyria (patchy involvement) –> “Smooth brain”
Macroscopic features:
* Numerous irregulary formed gyri –> Cobbelstone - like surface
* Many gyri
Microscopic features:
* A festooned cortex w/ fusion of Gyri
features of?
Polymicrogyria
Absence of the olfactory bulb is known as ?
Arrhinencephaly
* Mild form of Holoprosencephaly
Posterior Fossa Anomalies
1) Chiari Type I malformation
2) Arnold-Chiari (Chiari Type II) Malformation
3) Dandy-Walker Malformation
Macroscopic features:
* Low-lying cerebellar tonsils, extending through the
foramen magnum
* Protrusion of the tonsils into the foramen magnum
features of?
Chiari Type I malformation
Arnold-Chiari (Type II) Malformation Coexists w?
hydrocephalus and lumbar myelo-meningocele
Macroscopic features:
* Small posterior fossa
* Misshaped midline cerebellum
* Protrusion of tonsil and vermis below the foramen magnum
* Hydrocephalus
* Narrowing of the 4th Ventricle
* Elongation of the brain stem and Vermis
features of?
Arnold-Chiari Malformation
Macroscopic features:
* Enlarged posterior fossa
* Absence of the cerebellar vermis
* Large midline cyst
* Cystic dilatation of the 4th Ventricle
Microscopic features:
* Agenesis of the cerebellar Vermis
* Microgyri in the cerebral cortex
features of?
Dandy-Walker Malformation
Patho of Multiple Sclerosis:
* ————– -> Increased risk for MS
* Polymorphisms in the genes encoding receptors for ———-
* Increased Th17 and Th1 CD4+ cells
* Contribution from CD8+ T cells and B cells
- HLA-DR2 Variants–> Increased risk for MS
- Polymorphisms in the genes encoding receptors for IL-1 & IL-7
- Increased Th17 and Th1 CD4+ cells
- Contribution from CD8+ T cells and B cells
Macroscopic Features:
Characteristic lesions (“plaques”): Multiple, well circumscribed, slightly depressed, glassy-appearing, gray-tan, irregular shaped
features of?
Multiple Sclerosis
location of “Plaques” in Multiple sclerosis
- Paraventricular regions (most common)
- Optic nerves and chiasm
- Brain stem
- Cerebellum
- Spinal cord
Macroscopic Features:
* Diffuse gray and translucent colour of the white matter
* Decrease in the volume of the white matter –> Brain atrophy, Ventricular enlargement, Secondary changes in the gray matter
Microscopic Findings:
* Myelin loss
* Lipid stuffed macrophages
features of?
Leukodystrophies
Clinical presentation of Leukodystrophies
- Affected children –> Normal at birth, but developmental abnormalities manifested during infancy and childhood
- Deterioration in motor skills
- Spasticity
- Hypotonia
- Ataxia
Macroscopic features:
* Swollen and softened Pons and Medulla
Microscopic features:
* perivascular cellular infiltrate, composed of Macropahges and mononuclear cells
* Myelin loss associated w/ a perivascular macrophage infiltrate (Heidenhain stain)
features of?
Acute Disseminated Encephalo-Myelitis
Macroscopic features:
* Multiple scatterd petechial haemorrhages
Microscopic features:
* Multiple foci of inflammatory demyelination,
with diffuse oedema in the adjacent white matter
* Perivascular neutrophil infiltrates in cerebral white matter
features of?
Acute Haemorrhagic Leukoencephalitis
Microscopic features:
* Spinal Cord lesion with extensive destruction of the parenchyma
* Perivascular infiltrates of eosinophils and neutrophils
features of?
Neuro-Myelitis Optica (NMO)
CM of Central Pontine Myelinolysis
Rapidly evolving quadriplegia
(paralysis of the 4 limbs)
Central Pontine Myelinolysis is characterised by the development of ———-, induced by changes in osmotic pressure –> loss of ——- in the ——- of the ——–
Central Pontine Myelinolysis is characterised by the development of Oedema, induced by changes in osmotic pressure –> loss of Mylein in the center of the pons
Thiamine Deficiency –> ———
Wernicke Encephalopathy
Macroscopic Features:
* Foci of haemorrhage and necrosis, in the mamillary bodies and para-ventricular (3rd & 4th ventricles)
Microscopic Findings:
* Early lesions: Dilated capillaries with prominent endothelial cells Haemorrhages
* Late lesions: Cystic spaces with haemosiderin-laden macrophages
* Lesions in the medial dorsal nucleus of thalamus –> Association with Korsakoff syndrome
features of?
Wernick Encephalopathy Thaimine Deficiency
Microscopic features of Acute/Chronic Wernike’s Encephalopathy
Microscopic Findings:
* Astrocytes (Alzheimer type II cells) with swollen, pale nuclei in the cortex and basal ganglia
featurse of?
Hepatic Encephalopathy
Toxic Disorder caused by Lead?
Diffuse Encephalopathy
Toxicity from Aresnic causes?
Encephalopathy and peripheral Neuropathy (SensoryMotor Axonopathy)
Mercury Toxicity –> ——
Tremors, emotional changes, insomnia, muscle
atrophy, disturbances in sensations, changes in nerve responses, cognitive dysfunction
Methanol Toxicity –> ——-
Blindness
**
Carbon Monoxide Toxicity –> ——-
Hypoxic injury to the Globus pallidus
Ethanol Toxicity –> ——
Chronic alcoholism –> Atrophy in the anterior
cerebellar vermis –> Truncal ataxia, unsteady gait
and nystagmu
Ionising radiation toxicity –> ——
Headaches, nausea,
vomiting and papilloedema
Microscopic features:
* Large areas of coagulative necrosis,
* oedema and
* thick-walled vessels with intramural fibrin-like material
* Haemosiderin accumulation
* Extensive vascular hyalinisation
* Neurofibrillary tangles
features of?
Toxicity due Ionising radiation
Pathogenesis of Alzheimer Disease:
* Progressive accumulation of ———— in the brain
* —– leads to hyper-phosphorylation of —– –> Redistribution of tau from axons into dendrites and cell bodies –> Formation of ———–
- Progressive accumulation of beta Amyloid (Αβ) in the brain
-
Αβ leads to hyper-phosphorylation of Tau –> Redistribution of tau from axons into dendrites and
cell bodies –> Formation of tangles
Macroscopic Features:
* Variable degree of cortical atrophy –> Widening of the cerebral sulci and thinning of the gyri
* Hydrocephalus ex vacuo
* Neuritic and Diffuse Plaques (extra-cellular lesion)
* Neurofibrillary tangles (intra-cellular lesion)
features of?
Alzheimer Disease
Alzeheimer Disease
Microscopic Findings:
——————-:
* Paired helical filaments –> Basophilic fibrillary
structures in the cytoplasm of the neurons
* Abnormally hyper-phosphorylated tau protein –> Major component of paired helical filaments
* Localisation: Entorhinal cortex, hippocampus, amygdala, basal forebrain
Neuro-Fibrillary Tangles (NFTs)
Subtype of Fronto-Temporal Degeneration-tau ?
Pick disease
(characteristic smooth, globular, pale basophilic inclusions, [Pick bodies])
Macroscopic features:
* “Knife-like” thinning of the gyri
Microscopic features:
* Pick bodies
features of?
Pick disease
Macroscopic Features:
* Pallor of the substantia nigra and locus coeruleus
Microscopic Findings:
* Loss of the pigmented Neurons and gliosis in the above regions
* Presence of Lewy Bodies in the remaining neurons
* Lewy Bodies:
- Intra-cytoplasmic, eosinophilic, round inclusions with a dense core and a peripheral pale halo
- Composed of α-Synuclein, Neurofilaments and Ubiquitin
- Lewy Neurites: Dystrophic neurites containing abnormally aggregated α-Synuclein
features of?
Parkinson Disease
CF of Parkinson Disease
- Tremor
- Rigidity
- Bradykinesia
- Instability
Tx for Parkinson Disease
L-DOPA
Macroscopic Features:
* Small brain
* Prominent atrophy of the Caudate Nucleus, and less severe the Putamen
* Atrophy of the Globus Pallidus, secondarily
* Dilatation of the lateral and third ventricles
Microscopic Findings:
* Severe loss of neurons from Striatum
* Fibrillary gliosis
* Intra-nuclear inclusions (aggregates of ubiquition)
features of?
Huntington Disease
CM of Friedreich Ataxia
Amyotrophic Lateral Sclerosis is caused by mutations in the genes —– and FUS
TDP-43
CM of Amyotrophic Lateral Sclerosis based on loss of lower motor neurons
- Denervation of muscles
- Muscular atrophy
- Weakness
- Fasciculations
CM of Amyotrophic Lateral Sclerosis based on Loss of Upper motor Neurons
- Paresis
- Hyper-reflexia
- Spasticity
Macroscopic Features:
* Thin and gray anterior roots of the spinal cord
* Mildly atrophic pre-central gyrus (severe cases)
Microscopic Findings:
* Lwey body-like inclusions
* Degeneration of the lateral cortico-spinal tracts
* Reactive gliosis
* Loss of anterior root myelinated fibers
* Cytoplasmic inclusions (TDP-43 [+]), with exception the SOD-1 cases
* Hyaline inclusions
* Bunina bodies
features of?
Amyotrophic Lateral Sclerosis
Epidural Absces –> ————
Subdural Empyema
The 3 forms of Infectious Meningitis
1) Acute pyogenic (bacterial)
2) Aseptic (viral)
3) Chronic (Tbc)
cause of Acute Pyogenic Meningitis in neonants
E. coli, group B Streptococci
Cause of Acute Meningitis in adolescents and young adults
Neisseria meningitidis
Cause of Acute Meningitis in older individuals
Streptococcus pneumoniae and Listeria monocytogenes
CF of Acute Pyogenic Meningitis
1) Positive Kernig’s and Brudzinki signs
2) Neck stiffness
3) Vomiting
4) headache
5) Photophobia
6) Clouding of Consciousness
7) Irritablity
Macroscopic Features:
* Leptomeningeal exudate, over the surface
of the brain
* Engorged and prominent meningeal vessels
Microscopic Findings:
* Neutrophil cell infiltrates within subarachnoid
space
* Phlebitis and a thrombus
* Gram stain –> Pneumococcus meningitis- purulent exudate
featurse of?
Acute Pyogenic Meningitis
Macroscopic Features:
* Brain swelling
* subtle Hyperaemia
Microscopic Findings:
* Mild to moderate leptomeningeal lymphocytic infiltrate
features of?
Aseptic Meningitis
lab findings of Brain Abscess
- Increased numbers of white blood cells
- high protein levels
- Normal glucose content
Macroscopic Features:
* Discrete lesion
* Central liquefactive necrosis
* Surrounding fibrous capsule
Microscopic Findings:
* Granulation tissue and oedema around the necrotic core
* Zone of reactive gliosis, outside the fibrous capsule
features of?
Brain Abscess
Characteristic Histologic Features:
* Perivascular and parenchymal mononuclear cell infiltrates
* Microglial nodules
* Neuronophagia
* Presence of inclusion bodies
features of?
Viral Encephalitis
Important cause of Epidemic Encephalitis?
ARBO (ARthropod-BOrne) virus
CM of ARBO (Arthropod-borne) disease
- Seizures
- Confusion
- Delirium
- Stupor or Coma
- Reflex asymmetry
- Ocular Palsies
- yellow fever
Lab findings of ARBO (Arthropod-borne) viruses
CSF:
* Colourless
* Early neutrophilic pleocytosis –>Conversion
to lymphocytosis
* Elevated protein level
* Normal glucose
Microscopic Findings:
* Perivascular lymphocytic Meningoencephalitis
* Micro-Abscess in the white matter
* Multifocal gray and white matter necrosis
* Neuronophagia
* Microglial nodules
* Necrotising Vasculitis with focal haemorrhages
(severe cases)
features of?
Eastern Eqine Encephalitis
(ARBO Viruses)
**
Macroscopic Features:
* Inferior and medial regions of the temporal lobes
and the orbital gyri of the frontal lobes
* Heamorrhagic Necrosis in the Temporal and frontal lobe
Microscopic Findings:
* Necrotising and haemorrhagic infection
* Perivascular inflammatory infiltrates
* Large eosinophilic intranuclear viral inclusions
(Cowdry type A bodies)
features of?
HSV Encephalitis (caused by HSV-1)
Pathogensis and CM of Polio virus
* Subclinical or ————-
* Invasion of the CNS and destruction of the motor
neurons in spinal cord and brain stem (————–)
* Loss of motor neurons –> ———— and
————–, in the affected body region
* Paralysis of the respiratory muscles, in acute disease –> ———-
- Subclinical or mild Gastroenteritis
- Invasion of the CNS and destruction of the motor
neurons in spinal cord and brain stem (Paralytic Poliomyelitis) - Loss of motor neurons –> Muscle wasting and
hyporefelxia, in the affected body region - Paralysis of the respiratory muscles, in acute disease –> death
Microscopic Findings:
* Discrete, intra-cytoplasmic, deeply eosinophilic
inclusions within neurons (Negri bodies)
features of?
Rabies virus
Microscopic Findings:
* Predominantly, in subcortical white matter, diencephalon and brain stem
* Presence of microglial nodules, with multinucleate giant cells
* Abnormally prominent endothelial cells
* Perivascular foamy or pigment-laden macrophages
* Foci of tissue necrosis and reactive gliosis
* Multifocal or diffuse areas of myelin pallor, with axonal swellings and gliosis
* Identification of virus in CD4+ lymphocytes and multinucleate macrophages and microglia
features of?
HIV
Myelin in the White matter can be identified using which histochemical stain ?
LFB- Luxol Fast Blue
cause of Polymoa-Virus & Progressive multifocal leukoencenphalopathy
JC virus
Macroscopic Features:
* Patchy, irregular, ill-defined areas of white matter destruction
Microscopic Findings:
* Centrally localised lipid-laden macrophages and reduced number of axons
* In the periphery of the lesion, enlarged oligodendrocyte nuclei (Plum-coloured) with glassy-appearing amphophilic viral inclusions
* Bizarre giant forms of astrocytes (irregular, hyperchromatic, sometimes multiple nuclei)
features of?
Polymoa-Virus & Progressive multifocal leukoencenphalopathy
Morphology:
Proliferation of the organisms in the Virchow-Robin spaces –> Characteristic “soap bubble” like appearance
Features of?
Fungal Encepahlitis caused by Cyrptococcus Neofromans
Macroscopic Features:
* Multiple Abscesses in the gray-white junction and the deep gray nuclei (immunosuppressed individuals)
* Oedema
Microscopic Findings:
* Central foci of necrosis with small haemorrhages
and mixed inflammatory cell infiltrates and vascular
proliferation
* Free Tachyzoites and encysted Bradyzoites at the periphery of the necrotic foci
features of?
Cerebral Toxoplasmosis
cause of Cysticercosis
Taenia solium
Macroscopic Features:
* Cysts with a smooth lining, within the brain and subarachnoid space
Microscopic Findings:
* Body wall and hooklets from mouth parts
* Intense inflammatory infiltrate (with eosinophils) - incase of dead encysted organism
* Marked gliosis
features of?
Cysticercosis
Macroscopic Features:
* Little or no brain atrophy
Microscopic Findings:
* Spongiform changes in the cerebral cortex and deep gray matter structures (e.g. Nucleus caudatus, Putamen)
* Neurons w/ Microscopic vacuoles of variable size within the neuropil and neuronal perikaryon
* Severe cases:
* Severe neuronal loss
* Reactive (astro)gliosis
* Development of “status spongiosus”
features of?
Sporadic and Familial Creutzfeldt-Jakob disease
Vareint Cretzfeldet-Jakob disease specific microscopic diffrence from other CJD forms
Amyloid plaques
