Neuro Flashcards
1
Q
Epi/ Grading of pilocytic astrocytoma
A
Benign tumours; Grade I (WHO)
* Children and young adults
2
Q
Location of Pilocytic astrocytoma
A
* Cerebellum (most common)
* Third ventricle
* Optic pathways
* Spinal cord
* Cerebral hemispheres
3
Q
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 ?
A
Pilocytic astrocytoma (WHO GRADE 1)
4
Q
Epi of Diffuse Astrocytomas
A
80% of adult gliomas
5
Q
loc of Diffuse astrocytomas
A
Cerebral hemispheres
6
Q
Classification of Diffuse astrocytomas
A
1) Well-differentiated astrocytoma (WHO Grade II)
2) Anaplastic astrocytoma (WHO Grade III)
3) Glioblastoma (WHO Grade IV)
7
Q
Gentic predisposition of Diffuse Astrocytomas
A
1) Loss of function mutations in p53 and Rb genes (Glioblastomas)
2) Mutations in the IDH1and IDH2 genes (Low grade astrocytomas) –> Important diagnostic utility
8
Q
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?
A
Well-differentiated astrocytoma -WHO Grade II
9
Q
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?
A
Glioblastoma (WHO Grade IV)
10
Q
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?
A
Well- Differentiated Oligodendroglioma
11
Q
Loc of Epyndymoma
A
- Children and adolescents –> Near 4th ventricle
- Adults –> Spinal cord
12
Q
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?
A
Conventional Ependymoma (WHO GRADE II)
- Increased cell density, nuclear pleomorphism, high mitotic index, necrosis (Anaplastic Ependymomas)
13
Q
3 Examples of neuronal Tumours
A
1) Central Neurocytoma (low-grade)
2) Gangliogliomas (low-grade astrocytoma)
3) Dysembryoplastic Neuroepithelial Tumour (low-grade childhood tumour)
14
Q
loc of Central Neurocytoma
A
lateral or 3rd ventricles
15
Q
Microscopic Findings:
* Evenly spaced, round, uniform nuclei
* Often islands of neuropil
* Densely packed small- to medium- sized, round bland tumour cells
features of ?
A
Central neurocytoma
16
Q
CM of Gangliogliomas
A
Seizures
17
Q
loc of Dysembryoplastic neuroepithelial tumour (DNT)
A
Superficial temporal lobe
18
Q
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?
A
Dysembryoplastic Neuroepithelial Tumour (DNT)
19
Q
CM of Dysembryoplastic Nuro-Epithelial tumour (DNT)
A
Seizures
20
Q
Embryonal (Primitive) Neoplasms are known to have what distinctive appearance ?
A
Primitive “small round cell” appearance –> Resemblance to normal progenitor cells of CNS
21
Q
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?
A
Medulloblastoma
22
Q
Loc of Medulloblastoma
A
- Midline of the cerebellum (children);
- Lateral cerebellar tumours (adults)
23
Q
who is as high risk of developing primary CNS Lymphomas
A
immune-compromised individuals <> EBV [+]
24
Q
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?
A
Primary CNS lymphoma
25
Most common CNS germ cell neoplasm ?
Germinoma (resemblance to testicular Seminoma)
| * seminoma -> lymphocytic infiltrates
26
Loc of Germ Cell tumours
i. Pineal, ii. Supra-sellar regions
27
Loc of Meningioma
* Anywhere on the external surfaces of the brain (meninges)
* Within the ventricular system
28
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)**
29
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
30
Micro features:
* Combined features of **syncytial** and **fibroblastic** tumours
* **Psamoma bodies**
* **characteristic "Whorls"**
fetaures of what type of Grade I Meningioma?
Transitional Meningioma
31
micro features:
* Presence of numerous **psammoma bodies**
features of what type of Grade I Meningioma?
Psammomatous Meningioma
32
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
33
What stain is used for the identification e**osinophilic pseudo-psammoma bodies** in Secretory Meningioma ?
PAS ([+])
34
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)
35
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)
36
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
37
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)
38
A mononeuropathy Syndrom
| * peripheral nerve injury (single nerve)
Carpal Tunnel Syndrom
(compression of the median nerve)
39
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**
40
Epi of Schwannomas (Neurilemmomas)
* bening
* Sporadic (most common); 10% **associated with familial NF2**
41
loc of Schwannomas
* Soft tissues
* Internal organs
* Spinal nerve roots
* **Cranial nerves (Vestibular portion of the 8th nerve**
42
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 a**reas 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)
43
caues of Neurofibromatois Type 2
**Loss of function mutation of the NF2 gene** affecting **Merlin (Schwannomin) protein**
44
CF of NF2
**Bilateral vestibular Schwannomas** -> Hallmark of Neurofibromatosis Type 2
45
Hallmark of Neurofibromatosis Type 2?
**Bilateral vestibular Schwannomas**
46
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
47
localized Cutaneous Neurofibromas can exist as?
* solitary lesions or multiple in the context of NF1
* Superficial nodular or polypoid masses
48
Pathogonomic (symptom/sign) of NF1
**Plexiform Neurofibromas**
49
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
50
Diffuse Neurofibromas are ass w/?
NF1
51
Microscopic findings:
* Extensive infiltration of the dermis and subcutis
* **Subcuataneous masses**
* **Marked expansion of dermal tissue**
features of?
Diffuse Neurofibromas
52
Neurofibromatosis Type 1 is AKA?
Von Recklinghausen disease
53
who is likely to develop Malignant Peripheral Nerve Sheath tumours?
NF1 px
54
Cause of Conjuctivitis
**Adenovirus** (most common), bacteria
55
CM of Retinitis Pigmentosa
1) Retinal pigmentation
2) Peripheral vision loss **(“Tunnel vision”)** and progressive loss of Central Vision
56
patho of Senile Macular Degenration
Loss of central vision and pigmentary changes or haemorrhage in the macula
57
patho/CM of Angle-Closure Galucoma
Angle-Closure Glaucoma:
* Narrow anterior chamber angle
* Increase in intraocular pressure on dilatation of pupil
58
symptoms of open angle Glaucoma
1) Gradual loss of peripheral (side to side & up/down) visions, usually in both eyes
2) Tunnel vission
59
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)
60
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
61
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
62
what are the 2 types of cerebral odema
1) Vasogenic oedema
2) Cytotoxic oedema
63
Macroscopic Features:
* **Flattening of the gyri** and narrowing of the intervening sulci
* Compression of the ventricular cavities
features of?
**Cerebral Oedema**
64
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
65
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)
66
Compression of which artery is caused by Subfalcine (Cingulate) Herniation ?
**anterior cerebral artery**
67
microscopic features:
- Cortical spongious alteration
- **Peri-neuronal/ Peri-vascualar swelling of astrocytic processes**
features of?
Cytotoxic Cerebal Oedema
68
Compression ------------- nerve in a Transitional (Ucinate) Hernitation --> **Pupilary dilatation**
Third cranial nerve
69
In a Transtenotorial (Uncinate) Herniation , the compression of ----------- --> **Kernohan's notch**
Contralateral cerebral peduncle against the tentorium
70
In a Transtentorial (Uncinate) Herniation, the compression of ----------- -> **Ischaemic injury of the primary visual cortex**
**Posterior cerebral artery**
71
The 2 mechanisms that deprive O2 from the brain
1) Functional Hypoxia
2) Ischaemia due to tissue Hypoperfusion
72
cause of Global Cerebral Ischaemia
Severe systemic hypotension (as in cardiac arrest or shock)
73
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
74
What neuronal cells are affected by Global cerebral Ischaemia
* Pyramidal cells of hippocampus and neocortex
* Purkinje cells of the cerebellum
75
Immunohistochemistry used to stain Astrocytes
**GFAP**
76
Marker used for microglia staining
| * microglia --> macrophages of the brain
**CD68**
| * stains macropahges
77
cause of "Watershed infarcts"
**Hypotensive episodes**
(Anaphylactic shock, sudden blood loss, sever infections)
78
location of "Watershed infarcts"
The border-zone between the anterior and middle cerebral artery distributions
79
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
80
Most common site of embolic infarction
Middle Cerebral Artery (MCA)
81
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
82
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
83
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)
84
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
85
Histochemical stain for Beta Amyloid (in Cerebral Amyloid Angiopathy)
Apple-green birefringence on **Congo-red**
86
stain used for Haemosiderin (in Cerebral Amyloid Angiopathy)
**Pearl's/Prassin blue iron staining**
87
Pathologocial identifcation of cerebral Amyloid Angiopathy
1) Aβ immuno stain/ Congo red stain for Beta Amyloid
2) Pearl's blue iron stain for Haemosiderin
88
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
89
loactions of Subarachnoid haemorrhage & Saccular Aneurysms
~90% of Berry aneurysms in the anterior circulation
90
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
91
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**
92
the 4 types of Vascular Malformations
1) Arterio-Venous Malformations (AVMs)
2) Cavernous Malformations
3) Capillary Telangiectasias
4) Venous Angiomas
93
Epi of AVMs (Anter-venous mal.)
**Most common vascular malformation**
* M:F = 2:1; Age: 10-30 years
94
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)
95
loc of Cavernous Malformations
**Cerebellum, Pons**
96
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
97
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
98
Micro:
* Aggregates of ectatic venous channels
* Capillary Hindus resembles **the head of medusa**
features of?
Venous Angiomas (Varcies)
99
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
100
Contusion Will cause?
haemorrhage, tissue damage and oedema in the brain
101
Loc of a Contusion
1) Orbito-frontal regions
2) Temporal lobe tips
102
the 2 types of Contusion
Coup and Contre-Coup injuries
103
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
104
location of Diffuse Axonal injury (DAI)
* Near the angles of the lateral ventricles
* Corpus callosum
* Brain-Stem
105
Microscopic Findings:
* Axonal swellings **(“bulbs”)**, within hours of the injury
* Axonal **Spheroids**
* Immuno-histochemistry : **β-APP**
features of?
Diffuse Axonal injury
106
Histochemical stain for diffuse Axonal Injury ?
Silver stain
(detects axonal swelling)
107
Immuno-Histochemistry findings in Diffuse Axonal Injury
Amyloid Precussor Protein**APP**
108
Cause of Epidural Haematoma
Traumatic injury of the **middle meningeal artery,** after a skull fracture
109
causes of Subdural Haematoma
**Tear of the bridging veins**, after trauma
110
location of Subdural Haematoma
lateral aspects of the cerebral hemispheres
111
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
112
# ?? not sure if we need to know this
stain for Siderophages
Prussian-blue reaction
113
# ?? not sure if we need know this
Stain used for Erythrophagocytosis
Azan
114
# 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)
115
Which condition is known as **"Smooth brain"** ?
Lissencephaly
116
patho of Lissencephaly
**Total absence of gyration** or pachygyria (patchy involvement) --> **“Smooth brain”**
117
Macroscopic features:
* Numerous irregulary formed gyri --> **Cobbelstone - like surface**
* Many gyri
Microscopic features:
* **A festooned cortex w/ fusion of Gyri**
features of?
Polymicrogyria
118
Absence of the olfactory bulb is known as ?
Arrhinencephaly
| * Mild form of Holoprosencephaly
119
Posterior Fossa Anomalies
1) Chiari Type I malformation
2) Arnold-Chiari (Chiari Type II) Malformation
3) Dandy-Walker Malformation
120
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
121
Arnold-Chiari (Type II) Malformation Coexists w?
**hydrocephalus** and lumbar myelo-meningocele
122
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
123
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
124
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
125
Macroscopic Features:
**Characteristic lesions (“plaques”)**: Multiple, well circumscribed, slightly depressed, **glassy-appearing, gray-tan**, irregular shaped
features of?
Multiple Sclerosis
126
location of "Plaques" in Multiple sclerosis
* **Paraventricular regions (most common)**
* Optic nerves and chiasm
* Brain stem
* Cerebellum
* Spinal cord
127
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
128
Clinical presentation of Leukodystrophies
* **Affected children** --> Normal at birth, but developmental abnormalities manifested during infancy and childhood
* Deterioration in motor skills
* Spasticity
* Hypotonia
* Ataxia
129
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
130
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
131
Microscopic features:
* **Spinal Cord lesion** with extensive destruction of the parenchyma
* Perivascular infiltrates of **eosinophils and neutrophils**
features of?
Neuro-Myelitis Optica (NMO)
132
CM of Central Pontine Myelinolysis
Rapidly evolving **quadriplegia**
(paralysis of the 4 limbs)
133
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**
134
Thiamine Deficiency --> **---------**
**Wernicke Encephalopathy**
135
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
136
Microscopic features of Acute/Chronic Wernike's Encephalopathy
137
Microscopic Findings:
* **Astrocytes (Alzheimer type II cells)** with swollen, pale nuclei in the cortex and basal ganglia
featurse of?
Hepatic Encephalopathy
138
Toxic Disorder caused by Lead?
Diffuse Encephalopathy
139
Toxicity from Aresnic causes?
Encephalopathy and peripheral Neuropathy (SensoryMotor Axonopathy)
140
Mercury Toxicity --> **------**
Tremors, emotional changes, insomnia, muscle
atrophy, disturbances in sensations, changes in nerve responses, cognitive dysfunction
141
Methanol Toxicity --> **-------**
Blindness
142
# **
Carbon Monoxide Toxicity --> **-------**
Hypoxic injury to the Globus pallidus
143
Ethanol Toxicity --> **------**
Chronic alcoholism --> **Atrophy in the anterior
cerebellar vermis** --> Truncal ataxia, unsteady gait
and nystagmu
144
Ionising radiation toxicity --> **------**
Headaches, nausea,
vomiting and papilloedema
145
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
146
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**
147
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
148
# 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)**
149
Subtype of Fronto-Temporal Degeneration-tau ?
**Pick disease**
(characteristic smooth, globular, pale basophilic inclusions, **[Pick bodies])**
150
Macroscopic features:
* **"Knife-like"** thinning of the gyri
Microscopic features:
* **Pick bodies**
features of?
Pick disease
151
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
152
CF of Parkinson Disease
* Tremor
* Rigidity
* **Bradykinesia**
* Instability
153
Tx for Parkinson Disease
L-DOPA
154
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
155
CM of Friedreich Ataxia
156
Amyotrophic Lateral Sclerosis is caused by mutations in the genes **-----** and **FUS**
**TDP-43**
157
CM of Amyotrophic Lateral Sclerosis based on loss of lower motor neurons
* Denervation of muscles
* Muscular atrophy
* Weakness
* Fasciculations
158
CM of Amyotrophic Lateral Sclerosis based on Loss of Upper motor Neurons
* Paresis
* Hyper-reflexia
* Spasticity
159
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
160
Epidural Absces --> **------------**
Subdural Empyema
161
The 3 forms of Infectious Meningitis
1) Acute pyogenic (bacterial)
2) Aseptic (viral)
3) Chronic (Tbc)
162
cause of Acute Pyogenic Meningitis in neonants
E. coli, group B Streptococci
163
Cause of Acute Meningitis in adolescents and young adults
Neisseria meningitidis
164
Cause of Acute Meningitis in older individuals
Streptococcus pneumoniae and Listeria monocytogenes
165
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
166
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
167
Macroscopic Features:
* **Brain swelling**
* subtle Hyperaemia
Microscopic Findings:
* Mild to moderate leptomeningeal **lymphocytic infiltrate**
features of?
Aseptic Meningitis
168
lab findings of Brain Abscess
* **Increased numbers of white blood cells**
* **high protein levels**
* Normal glucose content
169
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
170
Characteristic Histologic Features:
* Perivascular and parenchymal mononuclear cell infiltrates
* **Microglial nodules**
* **Neuronophagia**
* Presence of **inclusion bodies**
features of?
Viral Encephalitis
171
Important cause of Epidemic Encephalitis?
**ARBO** (ARthropod-BOrne) virus
172
CM of ARBO (Arthropod-borne) disease
* Seizures
* Confusion
* Delirium
* Stupor or Coma
* Reflex asymmetry
* Ocular Palsies
* **yellow fever**
173
Lab findings of ARBO (Arthropod-borne) viruses
CSF:
* **Colourless**
* **Early neutrophilic pleocytosis** -->Conversion
to lymphocytosis
* Elevated protein level
* Normal glucose
174
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)
175
# **
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)
176
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**
177
Microscopic Findings:
* Discrete, intra-cytoplasmic, deeply eosinophilic
inclusions within neurons **(Negri bodies)**
features of?
Rabies virus
178
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
179
Myelin in the White matter can be identified using which histochemical stain ?
**LFB- Luxol Fast Blue**
180
cause of Polymoa-Virus & Progressive multifocal leukoencenphalopathy
JC virus
181
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
182
Morphology:
Proliferation of the organisms in the Virchow-Robin spaces --> Characteristic **“soap bubble”** like appearance
Features of?
Fungal Encepahlitis caused by **Cyrptococcus Neofromans**
183
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
184
cause of Cysticercosis
Taenia solium
185
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
186
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
187
Vareint Cretzfeldet-Jakob disease specific microscopic diffrence from other CJD forms
**Amyloid plaques**
