Pathology Flashcards
1
Q
What are 3 clinical presentations associated with ↑ICP?
A
1) Nausea
2) Headache
3) Altered conscious level
4) Papilloedema
2
Q
What is the clinical definition of raised ICP?
A
Increase in mean CSF pressure
- normal 7-15mmHg in supine adult
3
Q
What are 3 causes of ↑ICP?
A
Diffuse conditions:
1) Cerebral oedema
- infection
- infarction
- trauma
2) Hydrocephalus
Localised conditions:
3) Space-occupying lesions
- tumours
- haemorrhage/infarct
- abscess
4
Q
What is hydrocephalus?
A
Increase in CSF in CNS due to disturbance of formation, flow or absorption
- Normal 120-150ml
5
Q
What are the 2 types of hydrocephalus and how are they different?
A
1) Communicating
- between ventricles and subarachnoid space
- causes:
(i) venous drainage insufficiency (eg. thrombosis)
(ii) defective absorption (eg. SAH)
(iii) Overproduction (eg. meningitis)
2) Non-communicating
- obstruction between ventricular and subarachnoid space
- causes (eg.)
(i) congenital (eg. Arnold Chiari malformation)
(ii) mass lesions (eg. tumour, cysts, haematoma)
(iii) meningitis (via scarring, ventricular outflow obstuction)
6
Q
What are 3 complications of raised ICP?
A
1) Cerebral herniation
2) Loss of consciousness
3) Bradycardia
4) Hypertension
5) Neurogenic pulmonary oedema
7
Q
What is cerebral herniation?
A
The displacement of parts of the brain past rigid dural folds or through and opening into another compartment due to raised ICP
8
Q
What are 3 forms of cerebral herniation?
A
1) Subfalcine
2) Uncal(Transtentorial)
3) Tonsilar (“coning”)
9
Q
What is the (i) location (ii) cause and (iii) sequelae of subfalcine herniation?
A
i) Cingulate gyrus below falx cerebri
ii) cerebral hemisphere lesion
iii) usually clinically silent BUT
- can cause infarct (compression of anterior cerebral artery)
10
Q
What is the (i) location (ii) signs/sequelae of uncal (transtentorial) herniation
A
i) medial temporal lobe through tentorium cerebelli
ii)
a) Loss of consciousness
b) CNIII compression → ipsilateral fixed & dilated pupil
c) Posterior cerebral artery compression → cortical blindness
11
Q
What is the (i) location (ii) cause and (iii) sequelae of tonsillar herniation “coning”?
A
i) Cerebellar tonsils through foramen magnum
ii) posterior fossa SOLs
iii) neck stiffness, “coning”
- compression of cardiac and respiration centers in medulla and pons → cardiorespiratory arrest
12
Q
What is “coning” in cerebral haemorrhage?
A
Tonsillar herniation → compression of cardiac and respiration centers in medulla and pons → cardiorespiratory arrestc
13
Q
What are the 2 main pathogeneses of cerebrovascular disease?
A
1) Ischaemia and infarction
a) global hypoperfusion (eg. shock)
b) focal cerebral ischaemia (eg. thromboemboli)
2) Haemorrhage
a) Hypertension
b) Vascular malformations
c) Aneurysms
14
Q
What is the clinical definition of a stroke?
A
Neurologic signs and symptoms that can be explained by a vascular mechanism, have an acute onset, and persist beyond 24hrs
15
Q
What are 3 clinical manifestations of a stroke?
A
1) Localising signs (eg. hemiparesis)
2) Raised ICP (eg. haemorrhage, cerebral oedema)
3) Sudden severe headache (eg. ruptured vascular malformation)
16
Q
What are 6 risk factors for cerebrovascular accidents?
A
1) HTN
2) DM
3) Atherosclerosis
4) Transient Ischaemic Attacks (TIA)
5) Afib
6) Vascular malformations/abnormalities
7) Coagulopathies
17
Q
What is a transient ischaemic attack?
A
Temporary cerebrovascular insufficiency:
- transient episode of neurologic dysfunction caused by: focal brain, spinal cord or retinal ischemia
- NO acute infarction
18
Q
Where do watershed infarcts of the brain most commonly occur?
A
Areas between those supplied by middle and anterior cerebral arteries
19
Q
What does an intracranial watershed infarct result in?
A
Cortical pseudolaminar necrosis
20
Q
What are 3 causes of global hypoperfusion?
A
1) Cardiac arrest
2) Shock
3) Severe hypotension
21
Q
What is the pathogenesis of focal cerebral ischaemia?
A
Arterial occlusion due to thromboemboli resulting in reduced flow in a localised area of the brain
22
Q
What are 3 underlying causes of thromboemboli in focal cerebral ischaemia?
A
1) Atherosclerosis
2) Arteriosclerosis
3) Vasculitis
23
Q
What are 2 types of brain infarcts?
A
1) Pale/bland/non-haemorrhagic
2) Red/Haemorrhagic
24
Q
What is the clinical significance of differentiating pale and red infarcts?
A
Pale can be treated with thrombolytics unlike red (contraindicated)
25
How do the pathogenesis of pale and red infarcts differ in focal cerebral ischaemia?
Pale:
1) Thrombosis eg.
- atherosclerosis
- arteriolosclerosis
Red:
1) Venous Thrombosis
Emboli:
2) Carotid artery atheroma
3) Cardiac thrombi (post AMI, Afib, valvular disease)
4) Fat emboli (post bone trauma)
26
What form of necrosis is secondary to a cerebral infarction?
Liquefactive
27
How does the gross morphology of a pale infarct of the brain change over time?
48hrs:
- soft, swollen
- pale, indistinct grey-white matter junction
2-10D:
- gelatinous, friable
10D-3wks:
- liquid filled cavity
28
How does the histology of a pale cerebral infarct change over time?
12hr:
- ischaemic neuronal change (red neurons, oedema)
<48hrs
- Neutrophils
2D:
- foamy macrophages
1-3wks:
- ↑↑macrophages
- reactive gliosis (astrocytes)
29
What are the 4 causes of intracerebral haemorrhage?
1) Hypertension (smaller vessels)
- hyaline arteriolosclerosis
- fibrinoid necrosis
- charcot bouchard microaneurysms → rupture
2) Cerebral amyloid angiopathy
- amyloid deposition → weakened wall (leptomeningeal, cortical arterioles)
3) Structural vascular abnormalities
- Arteriovenous malformation
- Berry/saccular aneurysms (in circle of willis)
4) Coagulopathies
30
Which part of the brain do Charcot Bouchard microaneurysms most commonly occur?
Smaller vessels of the (i) Basal Ganglia and (ii) Thalamus
31
In which demographic are intracerebral haemorrhages due to structural vascular abnormalities seen?
Younger px
- sudden presentation
32
What are three effects of hypertension in the brain?
1) Lacunar infarcts
2) Hypertensive encephalopathy
3) Hypertensive intracerebral haemorrhage
33
What are lacunar infarcts and where do they most commonly occur?
Arteriolar sclerosis → occlusion → multiple small infarcts (lacunar infarcts <15mm)
Occur in:
deep penetrating vessels of basal ganglia, cerebral white matter, brainstem (eg. lenticular nucleus, thalamus, internal capsule, caudate nucleus, pons)
34
True or false: Lacunar infarcts are always a medical emergency.
False.
Site dependent
- may be clinically silent
35
What are the 2 main clinicopathologic entities in hypertensive encephalopathy?
1) Acute hypertensive encephalopathy (malignant hypertension)
2) Multi-infarct dementia
36
How are acute hypertensive encephalopathy/malignant hypertension and multi-infarct dementia different?
1) Clinical S/S:
MH: non-specific (headache, confusion, convulsion → coma)
MID: progressive dementia, gait abnormalities, focal neurological deficits
2) Pathogenesis:
MH: cerebral edema/herniation + petechial haemorrhages + fibrinoid necrosis of arterioles
MID: multifocal vascular disease (eg. thromboemboli)
37
Multi-infarct dementia is usually an (acute/progressive) condition affecting _______ age group.
Progressive
Middle aged to elderly (55-75y/o)
38
What is the most common cause of primary brain parenchymal haemorrhage?
Hypertensive intracerebral haemorrhage
39
What are the 3 forms of extra-axial intracranial haemorrhage?
1) Subarachnoid
- non-traumatic
- ruptured saccular aneurysms or arteriovenous malformations
2) Subdural
- traumatic
3) Epidural/extradural
- trauma
40
Which of the extra-axial intracranial haemorrhages are non-traumatic in aetiology?
Subarachnoid
41
What are 2 causes of subarachnoid haemorrhage?
1) Ruptured saccular (berry) aneurysms
2) Ruptured arteriovenous malformations
42
What is a "thunderclap headache" most commonly associated with?
Subarachnoid haemorrhage
43
What structure are berry aneurysms found on in an intracranial aneurysms?
Circle of Willis
- esp at junctions of communicating arteries
44
True or false: A "thunderclap" headache is a medical emergency.
True
a/w saccular "berry" aneurysm causing subarachnoid haemorrhage
- requires urgent surgical intervention (50% die w 1st bleed)
45
What genetic condition is associated with saccular aneurysms?
AD polycystic kidney disease
46
What are 4 forms of vascular malformations that increase a px risk of intracranial haemorrhage?
1) Arteriovenous malformation
2) Cavernous angioma
3) Capillary telangiectasis
4) Venous angioma
47
What are 2 intracranial complications of vascular malformations eg. arteriovenous malformations?
1) Intracerebral haemorrhage (CVA)
2) Subarachnoid haemorrhage
48
What does a laceration of the middle meningeal artery most likely lead to?
Epidural hematoma
49
What does a tear in the bridging veins in the subdural space most commonly lead to?
Subdural haemorrhage
50
What is the difference between the aetiology of a subdural and epidural haemorrhage?
Epidural
- laceration of artery (eg. middle meningeal)
Subdural
- venous bleed (eg. tear in subdural bridging veins)
51
What are 2 differences between acute and chronic subdural haematomas?
1) Cause
A: Acceleration-decelearion injuries → cerebral contusion (need rapid surgical decompression)
C: minor head trauma
2) Prognosis
A: high mortality rate
C: good prognosis
52
How would chronic subdural haemorrhage differ from an acute one on gross morphology?
Chronic: signs of organisation (fibrosis)
53
Which form of intracranial bleed is most likely in a temporal bone fracture?
Epidural haematoma (laceration of middle meningeal artery)
54
What is the classical clinical Hx of an epidural haematoma?
Head trauma
→ lucid interval
→ Sudden deterioration (eg. vomiting, restlessness, loss of consciousness)
55
What is a "lenticular (convex)" appearance on a head CT indicative of?
Epidural haemorrhage
56
What are 4 causes of intracerebral petechial haemorrhages?
1) Fat embolism (eg. after surgery)
2) Malaria
3) Vasculitis
4) Acute hypertensive encephalopathy
57
What are 2 conditions that are commonly associated with a ruptured berry aneurysm?
1) Polycystic kidney disease
2) Aortic coarctation
58
(Primary/secondary) tumours are more common in children.
Primary
59
What type of cells are arachnoid cells?
Meningothelial cells
60
What is the cellular origin of the meningiomas?
Menigothelial cells
61
What is the cellular origin of gliomas?
Glial tissue
62
What is the cellular origin of central neurocytoma?
Neurons
63
What is the cellular origin of medulloblastoma?
Embryonal
64
What are 2 cancers of the brain ventricles?
1) Choroid plexus tumours
2) Ependymomas (periventricular)
65
What are 3 cancers of brain parenchyma?
1) Medulloblastoma (embryonal)
2) Central neurocytoma
3) Gliomas
66
What are 3 brain tumours of midline structures?
1) Pituitary tumour
2) Germ cell tumours (children)
3) Pineal gland tumours
67
Meningiomas originate from _______________ cells usually occurring in the ________________ of the brain.
Arachnoid/Meningiothelial cells
Falx, cerebral convexities
68
Meningiomas are (common/rare), (fast/slow-growing) and may invade ___________.
Common and slow-growing
May invade skull bone
69
What syndrome is most common associated with meningiomas?
NF-2
70
Meningiomas are more common in (male/female) and the most common subtype is ___________________.
F > M
Commonest: Meningothelial type
71
What are 3 histological features of meningiomas?
1) Meningothelial whorls
2) Uniformed ovoid cells
3) Psammoma bodies
4) Nuclear inclusions
72
What are 3 forms of gliomas?
1) Astrocytoma
- WHO grade I-IV
2) Oligodendrogliomas
- WHO grade II-III
3) Ependymomas
- WHO grade II-III
73
What are the different types of astrocytomas?
1) Pilocytic (Grade I)
- children
- supra/infra-tentorial
2) Astrocytoma (Grade II-IV)
- IDH mutant
3) Glioblastoma (Grade IV)
- IDH wild-type
74
True or false:
IDH1 mutant gliomas are more favorable to wild type.
True.
Astrocytoma better prognosis than Glioblastoma
75
What is the histological appearance of pilocytic astrocytoma?
Astrocytes with long fibrillary cytoplasmic processes
76
Which demographic is most commonly afflicted with pilocytic astrocytoma?
Children
77
What are 2 histological characteristics of glioblastoma?
1) Palisading necrosis
2) Nuclear pleomorphism
78
What is the specific genetic profile of oligodendrogliomas?
IDH1 mutation and whole arm deletion of 1p and 19q
79
Which part of the brain is most commonly affected by oligodendrogliomas?
Cerebral cortex
80
True or false: Oligodendrogliomas are chemosensitive.
True
81
What is the histological appearance of oligodendrogliomas?
Uniformed round cells with "fried egg" appearance
82
Why does central neurocytoma cause raised ICP?
Near 3rd ventricle → compressive
83
Central neurocytomas usually affect ______ and have (good/poor) prognosis.
Adults
relative good prognosis
84
What is the difference between a CNS neuroblastoma and medulloblastoma?
Both aggressive embryonal brain parenchymal tumours in children
CNS neuroblastoma
- supratentorial
- poor prognosis
Medulloblastoma
- Medulloblastoma
- commoner
85
How are medulloblastomas classified?
According to molecular profile
- WNT and SHH activation status
- TP53 mutant/WT
86
What are the 2 treatment options for medulloblastoma?
Surgery and radiotherapy
87
Where do medulloblastomas commonly occur?
Cerebellum:
- Vermis (children)
- Hemispheres (adults)
88
Medulloblastomas are (aggressive/indolent) and spread via _______ causing ______________.
Aggressive
Spread via CSF → hydrocephalus
89
What are 3 histological features of medulloblastoma?
1) Sheets of small cells, high N/C ratio, mitoses
2) "Carrot shaped" nuclei
3) Rosettes
90
What are 2 histological features of ependymomas?
1) Perivascular pseudorosettes
2) True rosettes (canals)
91
What are ependymomas and where are they most commonly located (3)?
Gliomas of the ventricles
1) Periventricular
2) Intraparenchymal (supertentorial or infratentorial esp posterior fossa)
3) Spinal cord
92
What are 3 demographics that are most commonly seen with ependymomas?
1) Children (esp posterior fossa)
2) Young adults
3) NF-2 px
93
True or false:
Unlike medulloblastomas and choroid plexus tumours, ependymomas cannot cause hydrocephalus.
False.
All 3 can lead to hydrocephalus
94
What are the 2 forms of choroid plexus tumours?
1) Papilloma
2) Carcinoma (greater N/C ratio, cellularity)
95
What are 2 forms of sellar tumours?
1) Pituitary adenomas
2) Craniopharyngiomas
96
What are 2 forms of pituitary tumours?
1) Endocrine
- adenoma (commonest)
- carcinoma
2) Embryonal remnant tumours
- Craniopharyngiomas
97
What are 2 clinical effects of pituitary tumours?
1) Visual field defects
- optic chiasma compression → bitemporal hemianopia
2) Endocrine effects
- functional hypersecretion
98
Where do craniopharyngiomas arise from?
Tooth-forming epithelium within suprasellar region
99
Which 2 demographics are most commonly affected by craniopharyngioma?
1) Children
2) Adults (50s-60s)
100
What are the 2 types of craniopharyngiomas?
1) Adamantinomatous
2) Papillary
101
What is the gross appearance of an adamantinomatous craniopharyngioma?
Cystic, containing yellow viscous fluid ("engine oil" appearance)
102
What is the histological appearance of adamantinomatous craniopharyngioma (3)?
1) Cysts lined by stratified squamous epithelium
2) "Wet keratin"
3) Calcifications
103
What are 2 germ cell tumours of the CNS?
1) Teratoma
2) Germinoma
Less common:
3) Embryonal carcinoma
4) Yolk sac tumour
5) Choriocarcinoma
104
CNS germ cell tumours EPC:
Children () Adults
Males () Females
Pineal gland () Suprasellar region
Children > Adults
M > F
Pineal gland > Suprasellar region
105
What are 2 forms of pineal tumours?
1) Pineocytoma
2) Pineoblastoma
- high grade, primitive
106
Primary CNS lymphomas are mostly ________ in origin and are seen in ___________ px.
B cell, non-Hodgkin's
Immunosuppressed px (eg. AIDS → EBV lymphomas)
107
What are 3 histological features of schwannomas?
1) Spindled cells
2) Nuclear palisading
3) Hyalinised vessels
108
What are 3 examples of peripheral nerve sheath tumours?
1) Malignant
Benign:
2) Schwannoma
3) Neurofibroma
109
How are schwannomas different from neurofibromas?
Schwannoma
- well circumscribed/encapsulated
- attached to nerve
Neurofibroma
- non-encapsulated
- cutaneous/deep nerves
110
What is the histological appearance of neurofibroma?
1) Spindle cells within loose stroma
2) Collagen fibres within stroma
111
What are 4 examples of neurocutaneous syndromes?
1) Neurofibromatosis 1
2) Neurofibromatosis 2
3) Tuberous sclerosis
4) Von Hippel-Lindau Disease
112
Neurocutaneous syndromes often show a __________ inheritance pattern and present in _______________.
AD
Present:
- tumours
- Skin hamartomas
- nervous system
113
In NF1, the ____________ gene, which functions as a ______________, is mutated.
NF-1 gene for neurofibromin (17q)
- TS gene for signal transduction
114
What is the inheritance pattern of NF-1?
AD
115
What are 4 manifestations of NF-1 syndrome?
Neural tumours:
1) Neurofibromas (skin, CNVIII, radiculopathy, plexiform)
2) Optic nerve glioma
3) Hamartomas (Lisch nodules)
Other abnormalities:
4) Cutaneous
5) MSK
6) Renal
116
How does NF- progress to malignancy?
Sarcomatous transformation of neurofibromas → malignant nerve sheath tumours
117
NF2 is a result of a mutation in the _________ gene.
NF2 (Merlin) gene
118
What is the inheritance pattern of NF-2?
AD
- or de-novo mutation
119
How is NF-2 diagnosed?
At least 1 of:
1) Bilateral vestibular schwannomas
2) 1° wNF2 and
i) Unilateral vestibular schwannoma OR
ii) Any two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
3) Unilateral vestibular schwannoma and
i) Any two of: Meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
4) Multiple meningiomas and
i) Unilateral vestibular schwannoma OR
ii) Any two of: schwannoma, glioma, neurofibroma, cataract
120
In tuberous sclerosis, the __________ genes are mutated.
TSC1 and 2
- participate in cell proliferation
121
What are 4 manifestations of tuberous sclerosis?
1) Brain: cortical tubers, hamartomas
2) Skin: adenoma sebaceum, shagreen patch, ungual fibroma
3) Lung lesions
4) Renal angiomyolipomas
122
What is the inheritance pattern of tuberous sclerosis?
AD
123
What is the inheritance pattern of Von-Hippel Lindau syndrome?
AD
- variable penetrance
124
In Von-Hippel Lindau syndrome the __________ gene is affected.
VHL TS gene (3p25-26)
- angiogenesis + cell cycle
125
What are 5 manifestations of Von-Hippel Lindau Syndrome?
1) Hemangioblastomas
- retinal, cerebellar, supratentorial
2) Cysts
- renal, pancreatic, adrenal
3) RCC
4) Paraganglioma
5) Phaeochromocytomas
6) Endolymphatic sac tumour (inner ear)
126
What are 2 examples of paraneoplastic syndromes of the CNS?
1) Paraneoplastic cerebellar degeneration
2) Limbic encephalitis
127
What are 4 components of the Brain's natural barrier against infection?
Physical:
1) Skull
2) Dura mater
3) BBB
Cell:
4) Microglia
5) WBCs
128
What are 3 routes of CNS infection?
1) Local
- disruption of coverings (eg. trauma, spina bifida)
2) Regional
- sinusitis, otitis media, dental carries, facial infections
3) Blood borne
- septicemia
- septic emboli
4) Peripheral nerves
- rabies, HSV
129
What are 4 patterns of CNS infection involvement?
1) Meningitis
2) Subdural empyema, extradural abscess
3) Localised infection
4) Encephalitis
130
What are 3 clinical presentations of meningitis?
1) Headache
2) Fever
3) Neck Stiffness
4) Photophobia
131
What is the most common clinical presentation of encephalitis?
Altered mental state
132
What are 3 clinical presentation of an intracranial abscess?
1) Swinging fever
2) Localising signs of CNS disease
3) Raised ICP
- vomiting, LOC
133
What are 3 investigations for a CNS infection?
1) Imaging
- localise
Sterile samples:
2) CSF microscopy/culture/labs
3) Blood culture
134
What are 5 infective causes of meningitis?
Bacterial:
1) E. coli
2) Listeria cytomonogenes
3) H. influenzae
4) Neisseria meningitides
5) Strep pneumo
6) TB
Aseptic:
7) Echovirus
8) Coxsackie
Fungal:
9) Cryptococcus neoformans
10) Candida albicans
135
What are 2 bacterial causes of meningitis in neonates?
1) E. coli
2) Listeria monocytogenes
136
What is the main bacterial cause of meningitis in infants?
Haemophilus influenzae
137
What is the main cause of meningitis in adolescents?
Neisseria meningitides
138
What are 2 bacterial causes of meningitis?
1) Neisseria meningitides
2) Strep pneumoniae
139
Which part of the brain does TB usual infect?
Base of brain
140
What are 2 aseptic causes of meningitis?
1) Echovirus
2) Coxsackie
141
What are 2 fungal causes of meningitis?
1) Cryptococcus neoformans
2) Candida albicans
142
Which Ix is most important in the management of meningitis?
CSF exam (spinal tap)
143
What would the CSF of a px with meningitis show?
1) Cloudy
2) Cytology
- bacterial: ++polymorphs
- viral: lymphocytes++
- TB: either
144
What are 4 complications of meningitis?
1) Brain infarct
2) Meningeal fibrosis → hydrocephalus
3) Damage to cranial nerves
4) Raised ICP
5) Mental retardation (in children)
145
What are 2 gross features of tuberculous meningitis?
1) Gelatinous exudate on base of brain
2) White granules on tubercles (granulomas)
146
What are 3 complications of tuberculous meningitis?
1) Obliterative endarteritis
- cerebral ischemia, infarct
2) Fibrous adhesions in arachnoid mater
- cranial nerve deficits
- hydrocephalus
3) Tuberculoma of brain
147
Where do subdural empyemas usually originate from?
1) Skull infection
2) Paranasal sinus infection
148
What are 2 clinical manifestations of subdural empyema?
1) Local symptoms
- thrombophlebitis of bridging veins → localised infarct
2) Meningitis symptoms
- Headache, Fever, Neck Stiffness, Photophobia
149
How are subdural empyemas treated?
Surgical drainage
150
Where do extradural abscesses originate from?
1) Sinusitis
2) Iatrogenic
151
What is a condition that is commonly a/w extradural abscesses and what is the main concern with this condition?
Osteomyelitis
→ spinal cord epidural infection → cord compression
152
How do the aetiologies of single vs multiple cerebral abscesses differ?
Single:
- local source (otitis media, sinusitis, skull trauma, iatrogenic, facial infections, etc.)
Multiple:
- septicaemia, septic emboli (eg. infective endocarditis)
153
What are 4 common infective causes of cerebral abscesses?
Usually bacterial:
1) Strep
2) Staph aureus
3) Bacteroides
4) E. coli
154
What is the causative organism of neurosyphilis?
Treponema pallidum
155
What are 7 causes of localised infections in the CNS?
Bacterial:
1) Strep
2) Staph aureus
3) Bacteroides
4) E. coli
Spirochaetes:
5) Treponema pallidum
Fungal:
6) Candida spp.
7) Cryptococcus
8) Aspergillosis
Parasitic:
9) Toxoplasma gondii
10) Taenia solium
11) Amoeba (eg. Naegleria, acanthamoeba)
156
What is the typical imaging presentation of CNS toxoplasmosis?
Multiple ring-enhancing lesions on CT/MRI
157
In which demographic does CNS toxoplasmosis most commonly occur?
HIV+ px
158
Encephalitides are usually (bacterial/viral/parasitic/fungal/idiopathic)
Viral
159
How do the causes of encephalitides differ?
Acute: Acute meningoencephalitis
i) HSV, measles, CMV, HIV
ii) Fetal nervous system: rubella, CMV
Delayed / subacute:
a) Subacute sclerosing panencephalitis → Measles
b) Reactivation → VZV
Prion disease
160
Which virus(es) tend to target neurons and glial tissue?
1) HSV (esp temporal lobe)
2) Rabies
161
Which virus(es) tend to target motor neurons?
1) Poliovirus
2) Enteroviruses
161
Which virus(es) tend to target microglia?
HIV
161
Which virus(es) tend to target dorsal root ganglia?
VZV
162
What are 3 histological features of HSV1 encephalitis?
1) Cowdry type A nuclear inclusion
2) Tissue necrosis and haemorrhage
3) Perivascular lymphocytic infiltrates
163
Which demographics are most commonly afflicted with HSV1 encephalitis?
1) Children
2) Young adults (10% Hx of labial HSV)
164
What is common clinical presentation of HSV1 encephalitis?
Alteration in mood, memory, behaviour
165
Describe the pathogenesis of rabies.
Virus ascends from wound site → spinal ganglion → CNS → severe encephalitis (1-3mths depending on site)
166
How does rabies typically present?
Early: nonspecific
- malaise, fever, headache
- focal paraesthesia around wounds
Advanced:
i) marked CNS excitability
- painful touch, violent motor responses, convulsions
ii) pharyngeal muscle contraction when swallowing
- foaming, hydrophobia
iii) mania and stupor → coma and death
167
What is the characteristic histological finding in rabies?
Negri bodies
- cytoplasmic round/oval eosinophilic inclusions i
- in (i) pyramidal/hippocampal neurons (ii) purkinje cells (cerebellum)
168
Describe the pathogenesis of poliomyelitis.
Fecal-oral route → multiplies in lymphoid tissues (tonsils, peyer's patches, lymph nodes, etc.)
→ Viraemia
→ invade CNS
169
True or false: poliomyelitis is rarely self-limiting as it frequently penetrates CNS in viraemia.
False.
Most self-limiting inflammation of meninges, rarely penetrate CNS
170
What is the main complication/sequelae from poliomyelitis penetrating the CNS?
Damage motor neurons → flaccid paralysis + hyporeflexia
171
What are 2 types of CNS infections by HIV?
1) Aseptic meningitis
2) Encephalitis
172
How does HIV present in the spinal cord?
Vacuolar myelopathy
- holes in myelin sheath
- posterior columns
- corticospinal tract
173
How does CNS involvement of HIV present?
1) Imbalance
2) Sensory loss
3) Slowly progessive painless leg weakness, stiffness
174
What are 2 pathologies a/w HIV encephalitis?
1) Opportunistic infections in CNS (eg. toxoplasmosis, CMV, fungi, PML)
2) CNS lymphomas
175
What are 3 histological features of HIV encephalitis?
1) Multinucleated giant cells
2) Microglial nodules
3) Perivascular lymphocyte cuffing
176
What are 4 pathologies of neurosyphilis?
1) Tertiary syphillis
2) Meningovascular syphilis
3) Brain: general paresis of the insane
4) Spinal cord: tabes dorsalis
177
What are 2 histological features of meningovascular syphilis?
1) Granulomatous meningitis
2) Subintimal vessel thickening
178
How does neurosyphilis of the brain usually present?
Dementia
- neuronal loss
179
How does neurosyphilis of the spinal cord present?
Tabes dorsalis
- posterior column demyelination → charcot joints, skin damage
180
What are 3 CNS pathologies caused by fungi?
1) Vasculitis and thrombosis → infarction, hemorrhage
2) Meningitis (Cryptococcus)
3) Parenchymal invasion → abscess granulomas (Candia, Cryptococcus)
181
What are the modes of prion transmission?
1) Genetic
2) Sporadic
3) Transmissible
- contaminated transplantation tissue, food ingestion
182
What is the pathogenesis of prion diseases?
"Spreading"/accumulation of misfolded prion protein (PrP)
→ "Spongiform encephalopathy"
→ neuronal death
183
What are 2 histological features of prion disease?
1) Spongiform transformation
- cerebral cortex, deep grey matter
2) Amyloid deposits and plaques
184
What are 2 aetiologies for CNS malformations?
1) Prenatal/perinatal insult
a) Nutritional deficiency
- folate → neural tube defects
b) radiation → neural tube defects, anencephaly
c) infections, drugs, toxins, etc.
2) Genetics
185
What are neural tube defects and why are they pathogenic?
Failure of part of tube to close/re-opening of tube
→ abnormalities of neural tissue and overlying bone/soft tissue
186
Neural tube defects occur during ____________ of embryogenesis and can be detected in utero via ________.
3-4 week
Detected via:
- amniotic fluid and maternal blood
187
What is the main cause of spina bifida?
Folate deficiency
188
How can spina bifida be treated?
Folic acid (0.4mg) in periconceptional period
189
What are 3 neural tube defects?
Brain:
- anencephaly
- encephalocele
Spinal cord:
- spina bifida/spinal dysraphism
190
Anencephaly occurs in a ______ neural tube defect, (F M) and results in disrupted _________________________, sparing the ______________.
Anterior neural tube defect (F>M)
- disrupted forebrain development → absent brain and calvarium in the cerebrovasculosa
- spares posterior fossa
191
How does spina bifida present?
Occulta → hairy patch
Myelomeningocele/meningocele
- LL weakness/paralysis
- Skeletal abnormalities (club feet, hip dislocation)
- Bladder and bowels dysfunction, UTIs
- Pressure ulcers
192
What are 3 examples of forebrain abnormalities?
1) Polymicrogyria
2) Lissencephaly
3) Holoprosencephaly
193
How does polymicrogyria present?
1) Seizures
2) Mental retardation
3) Hemi/Quadriparesis
194
How does Lissencephaly present?
1) Dysphagia, aspiration
2) Seizures
3) Severe psychomotor retardation
195
How does holoprosencephaly present?
1) Facial midline abnormalities (eg. cyclopia)
2) Early mortality
3) Movement disorders
4) Feeding problems
196
What is the pathogenesis of holoprosencephaly?
Trisomy 13, maternal DM
→ incomplete separation of the cerebral hemispheres across midline
197
What are 2 examples of posterior fossa anomalies?
1) Arnold Chiari Malformation
2) Dandy Walker Syndrome
198
What is a Arnold Chiari Malformation?
Chiari type II malformation
- small posterior fossa
- cerebellar tonsils displaced through foramen magnum
199
What are 2 associations of Arnold Chiari Malformation?
1) Hydrocephalus
2) Spina bifida myelomeningocele
200
What are 3 clinical features of Arnold Chiari Malformation?
1) Headache especially on Valsalva maneouvre
2) Muscle weakness, fatigue
3) Brainstem damage/death
201
What is Dandy Walker Syndrome?
Enlarged posterior fossa
- cerebellar vermis absent/shrunken
- central open cyst
202
What are 4 clinical presentations of Dandy Walker Syndrome?
1) Slow motor development (infants)
2) Gradual skull enlargement
3) Raised ICP → vomiting, irritability, convulsion
4) Poor coordination, eye and face muscles
203
What are 4 neurodegenerative diseases?
1) Dementia
- eg. Alzheimer disease
2) Movement disorder
- eg. Parkinson disease (substantia nigra)
- Huntington Chorea (basal ganglia)
3) Motor weakness
- eg. Motor neurone disease
4) Others
- eg. spinocerebellar degenerations, Friedreich's ataxia, etc.
204
Describe 2 genetic predispositions in early onset Alzheimer disease?
1) Chromosome 21
- Amyloid Precursor Protein → Aß (ß amyloid peptides) deposition
2) Chromosome 19
- ApoE4 subtype → tau hyperphosphorylation
205
What are 3 clinical features of Alzheimer disease?
1) Progressive cognitive decline
2) Immobility
3) Pneumonia
206
What are 2 demographics that are most commonly afflicted by Alzheimer disease?
1) >80y/o (20%)
2) younger with Chromosome 21 APP or Chromosome 19 Apo E4 mutation
207
What is the the pathogenesis of Alzheimer's disease?
Abnormal protein deposition
i) amyloid (neuritic/senile) plaque
ii) Neurofibrillary tangles
→ neuronal damage and loss
208
What is the main gross feature of Alzheimer's disease?
Small, atrophied brain
- temporal lobe most affected
209
What are 2 histological features of Alzheimer's disease?
1) Amyloid/Neuritic/Senile plaques
- collections of dilated, tortuous neuritic process surrounding a core of ß amyloid
2) Neurofibrillary tangles
- hyperphosphorylated tau protein within neurons
210
What are 3 clinical features of Parkinson disease?
1) Rigidity
2) Slowing of voluntary movements
3) Rest tremor
211
Describe the genetic pathogenesis of Parkinson disease.
Disorder of α-synuclein gene → accumulation of α-synuclein protein → lewy bodies
212
What are 2 pathologies of Parkinson disease?
1) Loss of nerve cells from substantia nigra (midbrain)
- ↓ dopamine to basal ganglia
- pallor in substantia nigra
2) Lewy bodies in neuron
213
What is the gross appearance of Parkinson's disease?
Pallor in substantia nigra
214
What is the histological feature of parkinson's disease?
Lewy bodies in neurons
215
What are 4 clinical presentations of Huntington's Chorea?
1) Personality alterations
2) Cognitive decline
3) Abnormal movements
4) Death from aspiration, heart disease
216
What are 3 gross features of Huntington's Chorea?
1) Small brain with atrophy of caudate nucleus and frontal lobe
2) Atrophied putamen and globus pallidus (later)
3) Dilated ventricles
217
What is the inheritance pattern of Huntington Chorea?
AD
218
Describe the pathogenesis of Huntington's disease?
Mutattion in Huntingtin gene
→ ↑TNR → accumulation of Huntingtin protein in neurons of stratium (caudate nucleus, putamen) & cortex
→ atrophy + neuronal inclusions →
i) loss of striatal neurons → motor dysfunction
ii) loss of cortical neurons → cognitive decline
219
Why is Huntington's chorea associated with anticipation?
↑TNR → earlier age of onset
- Spermatogenesis → ↑TNR → paternal transmission a/w anticipation (early onset in next generation)
220
What are 7 metabolic/toxic causes of CNS disease?
Deficiencies
1) Vit. B1 (Thiamine)
2) Vit. B12
Storage Diseases:
3) Niemann Pick disease
4) Tay-Sachs disease
Hepatic encephalopathy (5)
CO poisoning (6)
Alcohol-related (7)
221
What CNS disease is caused by Vit. B1 defiency?
Wernicke encephalopathy
222
What disease is caused by Vit. B12 deficiency?
Subacute combined degeneration spinal cord
223
What are 2 CNS pathologies caused by CO poisoning?
1) Necrosis of globus pallidus
2) Diffuse cortical necrosis
224
What are 3 CNS pathologies caused by alcohol?
1) Fetal alcohol syndrome
- growth retardation, cerebral malformations
2) Acute intoxication
- respiratory depression → death
3) Chronic alcoholism
- cerebral cortical atrophy
- cerebellar atrophy
- Wernicke encephalopathy
- Korsakoff's psychosis
225
What is the pathogenesis of Thiamine deficiency CNS pathology?
Thiamine deficiency → damage to medial thalamus and mammillary bodies + generalised atrophy
226
What is Wernicke encephalopathy?
Acute development of psychotic symptoms of ophthalmoplegia
227
What is the gross appearance of Wernicke encephalopathy?
Hemorrhage and necrosis in mamillary bodies, walls of 3rd and 4th ventricles
228
What is Korsakoff's syndrome?
Chronic alcohol abuse characterised by:
1) Anterograde amnesia
2) Retrograde amnesia
3) Confabulation
4) Meager content in conversation
5) Lack of insight
6) Apathy
229
What is the gross appearance of Korsakoff's syndrome?
Cystic spaces with haemosiderin-laden macrophages
230
What are 3 presentations of Horner's syndrome?
Sympathetic system failure:
1) Flushing
2) Miosis
3) Anhidrosis
4) ±Ptosis
231
What is Harlequin's syndrome?
Unilateral blockade of the T2-T3 fibers carrying sudomotor and vasomotor supply
- asymmetric sweating and flushing on the upper thoracic region of the chest, neck and face
232
What are the neurological effects of a Pancoast tumour?
Apical lung tumour:
1) T1/lower brachial plexus lesions
2) Sympathetic outflow → anhydrosis
3) Phrenic nerve → hemidiaphragm paralysis
4) Recurrent laryngeal nerve → dysphonia
233
What are 3 conditions in which dorsal column involvement is seen?
1) B12 deficiency
2) Syphilis
3) Copper deficiency
234
What are 2 ways that Guillian-Barre may be life-threatening?
1) Type 2 Respi failure
2) Cardiac arrythmias
235
How is Guillain-Barre syndrome treated?
1) IVIG
2) Supportive
236
Why does Guillain Barre syndrome not cause wasting despite being a LMN disease?
Wasting takes too long, GBS is a one-off attack
237
How does hydrocephalus present in babies?
Enlarged/protruding fontanelles
