CNS / PNS Flashcards
A 20 year old woman has swollen bilateral basal ganglia and thalami. Which of the following veins is most likely thrombosed? (September 2013)
a. SSS
b. ISS
c. Internal cerebral vein
d. Cavernous sinus
e. Vein of Labbe
ANSWER: Internal cerebral vein
Which is not related to raised intracranial pressure? (March 2017)
a. Diffuse axonal injury
b. Posterior cerebral artery infarction
c. Anterior cerebral artery infarction
d. Kernohans notch
e. Duret haemorrhage
ANSWER: Diffuse axonal injury. The other options are complications of cerebral herniation.
What is true regarding hydrocephalus? (September 2013)
a. Non-communicating can cause rupture of the pineal recess
b. Normal pressure hydrocephalus is non-communicating
c. Hydrocephalus secondary to medulloblastoma is communicating
Hydrocephalus
o Communicating vs non-communicating
Communicating:
• With obstruction to CSF absorption
o Differentials include SAH, infectious meningitis & leptomeningeal carcinomatosis
• Without obstruction to CSF absorption
o Differentials include NPH, choroid plexus papillomas (overproduction of CSF)
Non-communicating (obstructive):
• Level of the foramen of Munro: colloid cyst, central neurocytoma, SEGA
• Aqueduct of Sylvius: aqueduct stenosis, tectal glioma
• 4th ventricle: posterior fossa tumour, cerebellar infarct, cerebellar haemorrhage
• May cause ballooning of the pineal recess
ANSWER: Rupture of the pineal recess is very uncommon, ballooning of the pineal recess of the third ventricle is seen in obstructive/non-communicating hydrocephalus
Which does not cause hydrocephalus? (August 2014)
a. Choroid plexus papilloma
b. Central neurocytoma
c. Ependymoma
d. Medulloblastoma
e. PXA
ANSWER: PXA does not typically cause hydrocephalus – it is a cortically based lesion
Which of these is true? (March 2015)
a. Pontine haemorrhage is associated with uncal herniation
b. Cingulate/subfalcine and …
c. Tonsillar herniation and Duret haemorhhage
d. Cingulate gyrus and PCA infarction
e. Uncal herniation and a 4th nerve palsy
Complications of subfalcine herniation:
o Contralateral hydrocephalus due to obstruction of the foramen of Munro
o ACA territory infarct due to compression of ACA branches
Complications of uncal herniation:
o Extensive brainstem ischaemia
o Duret haemorrhage: midline haemorrhage at the pontomesencephalic junction
- Damage to small branches of the basilar artery & draining veins at the time of rapid herniation
o Kernohan phenomenon/notch: indentation of the contralateral cerebral peduncle in the setting of uncal herniation
- Disturbs the descending corticospinal tract resulting in a hemiparesis ipsilateral to the expanding mass lesion (false localising sign)
o Compression of the ipsilateral PCA (homonymous hemianopia)
Complications of tonsilar herniation:
o Compression of the brainstem against the clivus, depression the respiratory & cardiac centres (loss of life sustaining centres)
ANSWER: Pontine haemorrhage is assoc w uncal herniation
Where is liquefactive necrosis most likely to occur? (August 2016)
a. Cerebral infarction
b. Cardiac infarction
Liquefactive necrosis is a type of necrosis which results in transformation of the tissue into a liquid, viscous mass
Assocations:
- Fungal & bacterial infections – often assoc w abscess formation in the CNS
- Hypoxic death of cells in the CNS (infarction)
• Reasons unclear why this pattern of necrosis predominates
• Lysosomes release digestive enzymes which liquefy tissues & destroy architecture
• A cyst wall is formed around the central necrotic debris
ANSWER: Cerebral infarction results in liquefactive necrosis
Regarding berry aneurysms, which is false? (March 2016, August 2016)
a. 25% infarct within 24 hours secondary to vasospasm
b. 90-95% arise from the carotid system
c. Ruptured aneurysm typically presents with headache and photophobia
d. Aneurysms are found in 2% of autopsy specimens
Berry aneurysms
o Cerebral aneurysms <25mm
- Distinct from microscopic (<300micrometres) Charcot-Bouchard aneurysms which develop as a result of chronic hypertension
- Appear mostly in the BG, thalamus, pons & cerebellum
o Multiple in 15-20%
- Familial – 30% of 1st degree relatives will have an aneurysm
Pathology:
- Rounded, lobulated focal outpouchings which most commonly arise at the bifurcations. Also can arise from the lateral wall
- Most are true aneurysms
- May become irregular & develop mural thrombus as they increase in size
- Ruptures occur in the region of the dome
Associated conditions: Ehlers-Danlos Marfan ADPKD Coarctation of the aorta Bicuspid aortic valve NF1 HHT Alpha-1 antitrypsin Cerebral AV malformation – may cause a flow related aneurysm FMD Thoracic & abdominal aortic aneurysms
Location: - Anterior circulation: 90% • ACA/ACommA – 0-40% • Supraclinoid ICA & ICA/PCommA junction: 30% • MCA bi/trifurcation: 20-30% - Posterior circulation: 10% • Basilar tip • SCA • PICA
Cerebral vasospasm:
o Major complication of SAH
- Has overtaken rebleed as the major cause of death & morbidity in patients treated for SAH
o Present on imaging in 40-70%
- Clinically apparent in 20-30%
- Typically occurs on the 4th to 10th days post bleed
Pathology:
- Not well understood but a number of agents are thought to play a role such as nitrous oxide, endothelin, oxyhaemoglobin & others
• Biochemical interactions & changes in gene expression are thought to account for the delay in symptom onset
• ?oxyhaemoglobin upregulates endothelin 1 which reduces the efficacy of nitrous oxide
- Alteration of normal vascular tone, causing narrowing of the large vessels
• Narrowing of smaller vessels which are in contact w CSF (but these are below the resolution of imaging)
Complications:
- Reduction in perfusion of brain parenchyma: ischaemic symptoms, infarction & its sequelae
Modified Fisher scale: Grade 0: • No SAH • No IVH • Incidence of vasospasm: 0% Grade 1: • Focal or diffuse, thin SAH • No IVH • Incidence of symptomatic vasospasm: 24% Grade 2: • Thin focal or diffuse SAH • IVH present • Incidence of symptomatic vasospasm: 33% Grade 3: • Thick focal or diffuse SAH • No IVH • Incidence of symptomatic vasospasm: 33% Grade 4: • Thick focal or diffuse SAH • IVH present • Incidence of symptomatic vasospasm: 40% - Thin <1mm, Thick >1mm
ANSWER: Vasospasm typically occurs after 4-10 days, w 20-30% developing clinically symptomatic vasospasm
Regarding cerebral haemorrhage, which is true? (September 2013)
a. In a patient with co-existent aneurysm and AVM, the aneurysm accounts for haemorrhage in about 50%
b. Hypertensive bleed in mainly in the frontal and temporal operculum
c. Aneurysms are mainly found in the lenticulostriate and pontine perforators
d. A 2cm aneurysm is more likely to rupture than a 1cm aneurysm
e. Cavernoma contains normal brain tissue
• Cavernomas are dilated vessels & loose stroma w no normal intervening brain tissue
ANSWER: A 2cm aneurysm is more likely to rupture than a 1cm aneurysm; AVMs & aneurysms are also equally likely to bleed (there was a comment that this could reflect two questions merged)
Which association is true? (March 2014)
a. Haemophilus influenzae in neonates
b. Corynebacterium diphtheriae and genitourinary
Haemophilus influenzae: o Causes: Pneumonia Bacteraeamia Meningitis Epiglottitis Septic arthritis Cellulitis Otitis media Purulent pericarditis
o Transmission:
- Respiratory droplets
- Most commonly affects young, unimmunized children & infants
Diptheria (Corynebacterium diptheriae):
o Gram negative rod
o Transmission: aerosol or skin secretions
Disease process:
- Oropharyngeal fibrinosuppurative exudate
- Bacteria grow in the membrane & release an exotoxin which injures the heart, nerves & other organs
Causes of acute pyogenic meningitis:
o Neonates: E. coli & group B strep
o Infants: Strep pneumonia, Haemophilis influenzae (reduced w immunization)
o Adolescents & young adults: Neisseria meningitides
o Elderly: Strep pneumonia & Listeria monocytogenes
ANSWER: Both of these options are false
What is the most common long term CNS complication of HIV/AIDS? (August 2016)
a. Primary CNS Lymphoma
b. Meningovasculitis
CNS affected by 4 mechanisms in HIV/AIDS:
o Direct consequence of the HIV virus
- HIV-associated dementia
- HIV vacuolar myelopathy
o Opportunistic infection
- Toxoplasmosis (most common)
- CMV
- Fungal infection: Cryptococcus, Candida, Aspergillus
- TB
- Neurosyphillis
- Progressive multifocal leukoencephalopathy (JC virus)
- Bacterial
o CNS tumours - Primary CNS lymphoma (2-6%)
o Treatment related complications - Immune reconstitution inflammatory syndrome (IRIS)
ANSWER: The most common longterm complication of HIV/AIDS from the list is primary CNS lymphoma
HIV infection is least associated with: (March 2014)
a. JC papovo virus
b. CMV virus
c. Toxoplasmosis
d. Cryptosporidium
e. Nocardia asteroids
AIDS defining illnesses:
o Infectious:
- Multiple or recurrent bacterial infections
- Candidiasis: oesophagus, bronchi, trachea or lungs
- Coccidiodomycosis: disseminated or extra-pulmonary
- Cryptococcosis: extrapulmonary
- Cryptosporidiosis: chronic intestinal
- CMV: other than liver, spleen or nodes - CMV retinitis
- HSV: chronic ulcers, bronchitis, pneumonitis, oesophagitis
- Histoplasmosis: disseminated or extrapulmonary
- TB or MAC: disseminated or extra-pulmonary
- PCP
- Recurrent pneumonia
- PML: JC virus
- Salmonella septicaemia: recurrent
- Toxoplasmosis
o Neoplastic:
- Invasive cervical cancer
- Kaposi sarcoma
- Lymphoma: Burkitt, immunoblastic or primary CNS
o Non-infections/non-neoplastic:
- HIV related encephalopathy
- LIP or pulmonary lymphoid hyperplasia
- Wasting syndrome of HIV
ANSWER: JC ‘papovo’ virus is not the correct name – assuming the recall meant JC virus, then nocardia would be the best answer
Which is most true regarding herpes encephalitis? (March 2016, August 2016, March 2017)
a. Haemorrhagic necrosis
b. HSV1 most common cause of viral meningitis in adults
c. HSV2 most common in children
d. Anterior and lateral temporal involvement is most common
e. 80% of patients will have a history of labral herpes
Herpes encephalitis:
HSV1 (90% of childhood & adult infections):
- Most commonly occurs in children & young adults
- Only 10% of affected patients have a PMHx of herpetic illness
Pathology:
• Starts in & most severely effects the inferior & medial regions of the temporal lobes + orbital gyri of the frontal lobes
• The infection is necrotizing & often haemorrhagic in the most severely affected regions of the brain
• Perivascular inflammatory infiltrates
• More diffuse involvement of the brain in slowly evolving infection
HSV2:
- Causes meningitis in adults & 50% of neonates born to women w active herpetic infection at the time of delivery
- Acute necrotizing & haemorrhagic encephalitis in patients w HIV
Pathology of infection:
- Intracellular virus - Infects the nasopharyngeal cells - Spreads to the trigeminal ganglion via the sensory branch of the lingual nerve - Can remain latent for extended periods of time. May never reactivate - Reactivation occurs in times of immunosuppression, trauma or other stressors
Causes of viral meningitis: o Enterovirus (90%) o Parechoviruses o Herpes viruses: HSV 1/2, VZV, EBV, CMV, HHV 6/7 o Arboviruses
ANSWER: HSV encephalitis causes haemorrhagic necrosis. HSV1 is the most common cause of encephalitis in adults and children (not meningitis).
Which of the following is not a characteristic imaging feature of acute herpes simplex encephalitis? (September 2013)
a. Sparing of the basal ganglia
b. Unilateral changes seen on MRI
c. Evidence of haemorrhage on MRI
d. Involvement of the limbic system
e. Mass effect
Imaging features of HSV encephalitis:
o Bilateral, asymmetric involvement of the limbic system, medial temporal lobes, insular cortices and inferolateral frontal lobes
- Typically spares the basal ganglia (which distinguishes features from an MCA infarction)
- Extralimbic involvement is more commonly seen in paediatric patients (especially parietal lobes)
- Involvement more diffuse in immunocompromised patients, particularly w increased involvement of the brainstem
o Cystic encephalomalacia may result as a long term consequence
CT features:
- Early scans may be normal - Subtle low density in the anterior & medial temporal lobes & insular cortex - Changes may progress & be complicated by haemorrhage - Patchy low level enhancement >1 week following onset
MRI features: T1: • Oedema • May be complicated by subacute haemorrhage T1+C: • Enhancement absent early • Enhancement pattern variable: (Gyral / Leptomeningeal / Ring / Diffuse enhancement) T2: • Hyperintensity of affected areas DWI/ADC: • Common due to cytotoxic oedema • Less intense restriction compared to infarction
DDx of HSV encephalitis:
o Limbic encephalitis (more commonly unilateral, can be a paraneoplastic syndrome)
o Gliomatosis cerebri
o Status epilepticus
o MCA infarction (typically involves the BG)
o Trauma
o Viral encephalitis: EBV, HHV-6, VZV, Influenza A, Rabies
ANSWER: Unilateral changes on MRI are not characteristic of HSV encephalitis
What is false regarding PML in the setting of HIV? (August 2016)
a. It is an opportunistic infection
Progressive multifocal leukoencephalopathy
o Demyelinating disease caused by the reactivation of JC virus in immunocompromised patients
Pathology:
- Usually from the reactivation of infection in a state of immunosuppression
• HIV patients – when the CD4 count drops < 100. JC virus infects the oligodendrocytes
o Confluent, bilateral but asymmetrical supratentorial white matter & thalamic involvement
- BG, brainstem & cerebellum can also be involved
- Most common in the subcortical frontal & parieto-occipital regions
Clinical presentation Altered mental status Motor deficits Limb & gait ataxia Visual symptoms Seizures Optic nerve & spinal cord typically spared
ANSWER: The provided answer is true – PML is an opportunistic infection caused by the JC virus
What is the aetiological agent in progressive multifocal leukoencephalopathy? (September 2013)
a. Jakob Creutzfeld virus
b. Measles virus
c. HIV virus
ANSWER: HIV virus is most correct, although it occurs in immunocompromised HIV patients secondary to reactivation of the JC (John Cunningham) virus in oligodendrocytes
What is the most common cause of SSPE (subacute sclerosing panencephalitis)? (August 2016)
a. Measles
Subacute sclerosing panencephalitis
o Rare, chronic progressive & fatal encephalitis which primarily affects children & young adults
o Caused by a persistent infection w immune resistant measles virus
- 1 in 100,000 people infected w measles
- Latency of 5-20 years
Clinical:
- Gradual progressive neuropsychological deterioration
- Personality change, seizures, myoclonus, ataxia, photosensitivity, ocular abnormalities, spasticity & coma
Pathology:
- Chronic measles virus infection causes similar changes to other chronic viral cerebral infections
ANSWER: Subacute sclerosing panencephalitis (SSPE) is assoc w measles
Which does not cause chronic meningoencephalitis? (March 2014)
a. Borelia burgdorferia
b. Listeria
c. Tuberculosis
d. Syphilis
Causes of chronic meningoencephalitis: o Tuberculosis: - CSF: mononuclear cell pleocytosis (occasional neutrophils), elevated protein, moderately reduced or normal glucose Complications: • Arachnoid fibrosis • Hydrocephalus • Obliterative end arteritis
Morphology of diffuse meningoencephalitis:
• Gelatinous fibrinous exudate w inflammatory cells in the subarachnoid space
• Less commonly, well formed granulomas at the base of the brain
- Obliterate the cisterna & encase the cranial nerves
- Obliterative endarteritis of the arteries running through the subarachnoid space
o Neurosyphilis:
- Manifestation of the tertiary stage of syphilis infection
• Occurs in 10% of patients w untreated infection
• HIV infected patients at increased risk, w increased severity & more rapid progression
- Meningovascular neurosyphilis:
• Chronic meningitis sometimes assoc w obliterative endarteritis
- Paretic neurosyphilis:
• Invasion of the brain by spirochetes, w neuronal loss & microglial proliferation
• Insidious loss of mental & physical capacity, progressing to severe dementia. Including ‘delusions of grandeur’ in the early stages
- Tabes dorsalis:
• Spirochete damage to the dorsal root sensory neurons
• Leads to impaired joint position sense, locomotor ataxia, loss of pain sensation w secondary skin & joint damage (including Charcot arthropathy)
• Absent deep tendon reflexes
o Neuroborreliosis:
- Neurologic manifestation of Lyme disease
- Variable presentation:
• Aseptic meningitis
• Facial nerve palsies & other polyneuropathies
• Encephalopathy
Microscopically: Microglial proliferation & scattered organisms
Other:
- Mycobacterium avium-intracellulare (in immunocompromised)
- Cryptococcus
ANSWER: Listeria is not assoc w chronic meningoencephalitis
Which of the following is not associated with Lyme disease? (August 2014)
a. Locomotor ataxia
b. Cranial nerve VII palsy
c. Radiculoneuritis
d. Aseptic meningitis
e. Encephalomyelitis
Lyme disease (Borrelliosis):
o Cutaneous: erythema migrans
o CNS: peripheral neuropathy, radiculoneuropathy, myelopathy, encephalitis, meningitis, facial nerve palsy
o Cardiac: myopericarditis, cardiac arrhythmia
o MSK: Lyme arthritis
ANSWER: Locomotor ataxia is not assoc w Lyme disease (is assoc w neurosyphilis)
A patient with rheumatic fever has a constellation of symptoms suggesting systemic embolization. They also have symptoms of headache and meningism. What is the most likely finding on MRI of the brain? (March 2016)
a. Ring enhancing cerebral lesions
b. Leptomeningeal enhancement and nodularity
ANSWER: Ring enhancing cerebral lesions – this suggests cerebral abscesses secondary to microemboli
Which disease is not associated with a prion? (March 2014)
a. Kuru
b. CJD
c. SSPE (subacute sclerosing panencephalitis)
ANSWER: SSPE is not a prior disease, it is assoc w measles
Which of the following does not demonstrate spongiform pathology? (March 2015)
a. Creutzfeld-Jakob disease
b. Kuru
c. Fatal familial insomnia
d. Gerstmann-Straussler-Scheinker
e. Variant Creutzfeld-Jakob disease
Prion diseases include: o Creutzfeld-Jakob disease o Gerstmann-Straussler-Scheinker o Fatal familial insomnia o Kuru
As per Robbins, all of these conditions demonstrate “spongiform change” except FFI
o Intracellular vacuoles in neurons & glia
o Lead to a clinically rapidly progressive dementia.
Caused by ‘spreading’ of the misfolded prion protein
o Familial spread seen in CJD, GGS & FFI
CJD – sporadic in 90%
o Cases of iatrogenic transmission from neuroSx & contaminated growth hormone
o Mean survival 7 months from symptom onset
vCJD:
o Differences to classic CJD:
- Younger patients
- Behavioural problems occur earlier
- Neurologic symptoms progress more slowly
o Linked to consumption of beef contaminated w bovine spongiform encephalopathy & blood transfusions
Fatal familial insomnia:
o Sleep disturbances characterise the initial phases
o May occur in tandem w CJD because of the pattern of mutations
o Can occur in a sporadic form (fatal sporadic insomnia)
o Disease course <3 years
ANSWER: Fatal familial insomnia does not cause spongiform change
What is the most likely presentation of prion disease? (March 2016)
a. Quick progression of dementia with motor and sensory dysfunction
b. Affects the basal ganglia and gyri early
CJD:
o Sporadic in 90%, others familial or iatrogenic
Presentation:
- Subtle memory or behavior problems
- Followed by a rapidly progressive demential
- Involuntary jerking muscle contractions
- Fatal 7 months following diagnosis
vCJD: o Linked to BSE Presentation: - Early behavioural manifestations - Slower neurological progression
Morphology:
o Spongiform changes in the cerebral cortex & deep grey matter (caudate & putamen) are characteristic. Primary motor cortex is characteristically spared
o Advanced cases have severe neural loss, reactive gliosis
o Severe advanced cases may have expansion of vacuolated areas into cyst-like spaces (status spongiosus)
o No inflammatory infiltrate
ANSWER: Prion disease affects the basal ganglia & gyri early
Which is false? (March 2016)
a. ADEM is caused by bacterial infection
b. There is 70% associated mortality with haemorrhagic ADEM
c. NMO is related to aquaporin 4 antibodies
d. Central pontine myelinolysis is caused by treatment of hyponatraemia
e. Demyelination can be a cause of internuclear ophthalmoplegia
ADEM:
o Monophasic illness of acute inflammation & demyelination 1-2 weeks following a viral illness or vaccination (<5%)
- Monophasic illness, but may have lesions at different stages evolving over a period of weeks
o Involves grey matter (esp BG) & spinal cord (lesser extent)
Epidemiology:
- Can occur at any age but most commonly in children & adolescents <15 yoa
- May be a slight male predominance
Pathology:
- Cross reactivity to viral antigens, causing autoimmune attack on the CNS
- Assoc w anti-MOG (myelin oligodendrocyte glycoprotein)
- Perivenular inflammation w sleeves of demyelination similar to MS. Lacks the infiltration of macrophages seen in MS
Internuclear opthalmoplegia:
o Clinical syndrome of impaired adduction in one eye w dissociated horizontal nystagmus of the other abducting eye
o Lesion in the medial longitudinal fasciculus (ipsilateral to the eye which cannot adduct)
Aetiology: Multiple sclerosis (most common) NMO Uncal herniation SLE Trauma Chiari malformation
ANSWER: ADEM typically follows a viral infection or vaccination, not a bacterial illness
Which does not show Parkinsonian features? (March 2015)
a. Progressive supranuclear palsy
b. Huntington disease
c. Multisystem atrophy
d. Lewy body dementia
Other disorders which demonstrate Parkinsonian features:
o MSA-P (Striatonigral degeneration)
o Dementia w Lewy bodies – dementia precedes or accompanies Parkinsonian features
o Wilson disease – pseudo-parkinsonian & cerebellar symptoms
o Progressive supranuclear palsy
o Ethylene glycol toxicity
Huntington’s disease features: o Progressive rigidity o Choreoathetosis o Dementia o Psychosis o Emotional lability o Juvenile form: cerebellar symptoms, rigidity & hypokinesia
ANSWER: Huntington disease does not show Parkinsonian features
Which is true regarding Pick disease? (March 2014)
a. Anterior parietal lobe atrophy
b. Asymmetric frontal and temporal lobe atrophy
c. Substanstia nigra atrophy
d. Cerebellar atrophy
Frontotemporal dementia/Pick disease:
o Neurodegenerative disease
- Tauopathy
- Characterised by the accumulation of Pick bodies
Epidemiology: Male predilection; 40-60 years
Characteristic features on pathology: Pick bodies Swollen chromatolytic neurons Loss of large pyramidal neurons Astrocytic gliosis
Radiographic features:
- Cortical atrophy of the frontal & temporal lobes
- Asymmetric, affect one region more than another
- Caudate head volumes often reduced
Frontotemporal lobar degeneration:
o Group of neurodegenerative disorders which are characterized by focal atrophy of the frontal & temporal cortices
- Not all tauopathies
- Distinct from Pick disease
Divided as:
- Behavioural variant frontotemporal lobar degeneration dementia
- Language variant frontotemporal lobar degeneration
• Agrammatic variant primary progressive aphasia
• Semantic variant primary progressive aphasia
• Logopaenic variant primary progressive aphasia
ANSWER: Asymmetric lobar frontal & temporal atrophy characterizes Pick disease
Regarding CADASIL, which is the least likely finding? (March 2016)
a. Large haemorrhagic infarcts
b. Caused by the NOTCH3 mutation
c. Involves the perforators and lenticulostriate vessels
CADASIL:
o Cerebral AD arteriopathy w subcortical infarcts & leukoencephalopathy
o AD microvasculopathy characterized by recurrent lacunar & subcortical white matter ischaemic strokes & vascular dementia
o Young & middle aged patients (30-50years) w/out known risk factors
- Disproportionate cortical hypometabolism
Presentation: Similar to migraine (+/- aura) Depression Psychosis Pseudobulbar palsy Focal neurological deficits Seizures
Imaging:
CT: white matter regions of low attenuation
MRI:
• Widespread confluent white matter hypointensities
o Superficial & deep white matter
- More circumscribed lesions in the BG, thalamus & pons
Initial disease:
• Anterior temporal lobe, external capsule & paramedian superior frontal lobe is classic
• Sparing of the occipital, orbitofrontal subcortical white matter, sub-cortical U-fibres & cortex
Cerebral microhaemorrhages in 45%. No characteristic distribution. Eventual cerebral atrophy => Corresponds to cerebral decline
DDx:
- Multiple early age infarcts from a hypercoagulable state
- MELAS
- Primary angiitis
- Subcortical arteriosclerotic encephalopathy (SAE)
- Susac syndrome
o Can be diagnosed by skin biopsy
ANSWER: Large haemorrhagic infarcts are not typical of CADASIL; small microhaemorrhages are present in 45%
Which is the least likely area of involvement in CADASIL? (March 2017)
a. Skin
b. Superior frontal lobe white matter
c. Temporal lobes
d. External capsules
e. Basal ganglia
ANSWER: Frontal lobe sparing (esp the orbitofrontal cortex, subcortical U-fibres & cortex); CADASIL is diagnosed by skin biopsy.
Which disorder could not have dilated perivascular spaces? (March 2014)
a. Trauma
b. Cryptococcosis
c. Mucopolysaccharidosis
d. Metachromatic leukodystrophy
ANSWER: Metachromatic leukodystrophy does not have dilated perivascular spaces
Which demonstrates X-linked recessive inheritance? (March 2014)
a. Adrenoleukodystrophy
b. Metachromatic leukodystrophy
c. Alexander disease
d. Canavan disease
- Adrenoleukodystrophy: X-linked recessive
- Metachromatic leukodystrophy: AR, lysosomal storage disease
- Alexander disease: sporadic dominant mutation in glial fibrilliary acidic protein
- Canavan disease: AR, neurodegenerative leukodystrophy
ANSWER: Adrenoleukodystrophy demonstrates x-linked recessive inheritance
Which is a mitochondrial inherited disorder? (August 2014)
a. Adrenoleukodystrophy
b. Alexander disease
c. Hurler syndrome
d. Leigh syndrome
e. Tay-Sachs disease
- Adrenoleukodystrophy: X-linked recessive
- Alexander syndrome: sporadic fibrinoid leukodystrophy
- Hurler syndrome: AR
- Leigh syndrome: mitochondrial
- Tay-Sachs disease: AR
ANSWER: Leigh syndrome is a mitchondrial disease. Others include Kearns disease & MELAS
Deficiency of which of these vitamins does not cause neurological issues? (August 2014)
a. B1 (thiamine)
b. B2 (riboflavin)
c. B3 (niacin)
d. B12
e. Vitamin E
B1: Wernicke-Korsakoff syndrome
o Clinical triad: acute confusion, ataxia, ophthalmoplegia
o Aetiology: alcohol abuse (90%), starvation/fasting, prolonged TPN w/out supplementation
o MRI: increased FLAIR/T2 in the mammillary bodies, dorsomedial thalami, tectal plate, periaqueductal grey matter, around the third ventricle
o Treated w IV thiamine supplementation - 20% mortality if untreated
B2: No associated neurological conditions
o Stomatitis, scaly skin rash, eye symptoms
o Deficiency may impair the absorption of iron
B3: 4Ds
o Dermatitis: brown discolouration of the skin in sun-exposed areas
o Diarrhoea: intractable diarrhoea, stomatitis, glossitis
o Dementia: pellagrous encephalopathy – apathy, memory loss, disorientation, depression or delirium
o Death
B12:
o Subacute combined degeneration of the spinal cord:
- Clinical: parasthesias of the hands & feet, progression to sensory loss, gait ataxia & distal weakness (especially in the legs)
Causes:
- Pernicious anaemia, Crohn disease & other causes of terminal ileitis
- Malnourishment, vegan diet
MRI: bilateral high signal w/in the dorsal columns
- Begins as an inverted V sign
- Typically begins in the upper thoracic region, with changes moving superiorly or inferiorly
- May be accompanied by cerebral white matter changes
DDx: Copper deficiency can look identical
Treatment: Correction of B12 deficiency. Half will completely recover with treatment
Vitamin E:
o Rare outside of premature infants
o Associated w spinocerebellar ataxia, myopathies & other neurological symptoms due to poor conduction of electrical impulses along the nerves & changes in nerve structure & function
ANSWER: Vitamin B2 is not assoc w neurological issues
Which is false of toxic effects on the CNS: (March 2015)
a. Ethanol causes cerebellar damage
b. Methanol causes hippocampal damage
c. Carbon monoxide affects the globus pallidus
d. Radiation and methotrexate are associated with leukoencephalopathy
Chronic ethanol abuse:
o Wernicke-Korsakoff syndrome
o Alcoholic cerebellar degeneration
o Multiple vitamin deficiencies: Thiamine/B1, Folate/B9, B6, B12
Methanol toxicity – toxic leukoencephalopathy:
o Putaminal necrosis
- Cystic cavities may develop in the putamen in chronic cases
o Other acute signal changes in the optic nerves, subcortical white matter, cerebellum
Carbon monoxide:
o Globus pallidus most commonly affected
o Changes are usually bilateral
Methotrexate-related leukoencephalopathy:
o Uncommon, can present as an acute or chronic process
- Most commonly occurs in paediatric patients undergoing Tx for ALL
- Can occur in any patient who has been administered methotrexate
- Dose dependant
o No specific established radiological features, but often has involvement of the centrum semiovale
White matter complications of brain radiotherapy:
o Treatment-induced leukoencephalopathy
o Coagulative necrotic leukoencephalopathy
ANSWER: Methanol does not cause hippocampal damage, it most commonly causes putaminal necrosis
Which is a WHO grade I lesion? (August 2014)
a. DNET
b. Ganglioglioma
c. Ependymoma
d. Central neurocytoma
e. Pilomyxoid astrocytoma
ANSWER: Both DNET & ganglioglioma are considered WHO grade I lesions by the latest criteria.
Note, previously DNET was the only tumour/option which was considered solely grade I
What is the most common cause of a paediatric hypothalamic solid tumour? (September 2013)
a. Pilocytic astrocytoma
b. Craniopharyngioma
c. Ependymoma
Astrocytoma:
o Most common neoplasm of the hypothalamic-optic chiasm region
o Usually low grade (pilocytic > fibrillary)
o Usually in children <5 years
o Endocrine dysfunction in 20%
o 20% of patients w pilocytic astrocytoma of the hypothalamus have NF1
ANSWER: Pilocytic astrocytoma is the most common cause of a paediatric hypothalamic solid tumour
What is not typical of a pilocytic astrocytoma? (September 2013)
a. Solid
b. From the cerebellar hemispheres
c. Does/doesn’t differentiate into a higher grade
Pilocytic astrocytoma:
o Typically a cystic cerebellar mass w an enhancing mural nodule. Well circumscribed w little / no oedema
o Most common primary brain tumour in children
o > 70% 20 year survival
Locations:
- Cerebellar 60% - Optic nerve/chiasm 25-30%. 1/3 assoc w NF1 - Adjacent to the third ventricle - Brainstem
ANSWER: Do not differentiate into higher grade lesions in the absence of radiation therapy; most commonly a cystic lesion (cerebellum) but 40% are solid lesions (optic chiasm, hypothalamus, brainstem)
Which is not a WHO grade I lesion: (September 2013)
a. Pleomorphic xanthoastrocytoma
b. Pilocytic astrocytoma
c. Subependymal giant cell astrocytoma
d. Choroid plexus papilloma
e. Ganglioglioma
ANSWER: PXA is not a WHO Grade I lesion, it is WHO Grade II
Regarding ependymomas in childhood, which is true? (September 2013)
a. By the time of diagnosis, has usually extended into the cisterna magna
b. Produces hydrocephalus by CSF production
c. In adults, is usually a supratentorial tumour
Supratentorial ependymomas
o 1/3 of ependymomas - 45-65% are extraventricular
- If intraventricular, 3rd ventricle > lateral ventricle
o Majority of adult supratentorial ependymomas are WHO Grade III lesions
- If present in children under 3, assoc w a very poor outcome
General features: Large complex appearing mass Mixed solid & cystic Hemispheric location more commonly Calc & intratumoral haemorrhage common Moderate but inhomogenous enhancement Larger at presentation (usually >4cm)
ANSWER: In adults, ependymomas are more commonly a supratentorial tumour
Which is true: (March 2015)
a. Myxopapillary ependymoma is classified as a WHO grade I/IV
b. Ependymoma of the spinal cord most commonly occurs in the elderly
c. Subependymoma occurs in the 4th ventricle
Myxopapillary ependymoma
o Variant type of spinal ependymoma which occurs exclusively in the conus medullaris & filum terminale
- 13% of spinal ependymomas
- Most common tumour of the conus & filum terminale
Epidemiology:
- Present earlier (mean age 35) - Slight male predominance
Prognosis:
- Usually slow growing
- 98% 5 years survival w complete resection
- Rarer aggressive tumours metastasize to LNs, lung & bone
- Some seed into the adjacent subarachnoid space
- Resection is often incomplete & local recurrence is common
- WHO grade I
Spinal ependymomas:
o Most common intramedullary neoplasm in adults - 60% of glial spinal cord tumours
o Second most common intramedullary lesion in children (30%)
Epidemiology:
- Mean age at presentation 39 - Male predominance - Associated w NF2
Six histological types: Cellular (most common) Papillary Clear cell Tanycytic Myxopapillary (filum & conus) Melanotic (least common) o WHO grade II & III - Except myxopapillary (grade I)
Subependymomas:
o Rare, benign tumours
o Slow growing & non-invasive - WHO grade 1
Epidemiology:
- Usually an incidental finding
• Rare presentations secondary to obstructive hydrocephalus
- Middle aged / older patients (5th and 6th decades)
- Slight male predominance
- More common in TS
- Distinguished from SEGAs, as are usually <2cm
Location:
- 4th ventricle – 50-60%
- Lateral ventricles – 30-40% (Usually frontal horns)
- 3rd ventricle & central canal of the spinal cord – rare
ANSWER: Subependymomas typically occur in the 4th ventricle. Myxopapillary ependymomas are WHO grade 1 lesions.
What is not a cause of epilepsy? (March 2015)
a. Central neurocytoma
b. JPA
c. Ganglioglioma
d. PXA
e. DNET
Tumours which have been implicated as a cause of epilepsy:
o Gangliogliomas
o PXA
o DNET
o Low-grade gliomas
o Central neurocytomas if there is extraventricular extension
• JPAs typically present in the posterior cranial fossa w raised ICP, cerebellar or bulbar symptoms
ANSWER: JPA is unlikely to present w epilepsy
Which is most commonly cortically based? (September 2013)
a. Low grade astrocytoma
b. Neurocytoma
c. DNET
d. Glioblastoma
ANSWER: DNET
A child has a tumour involving the cerebellum. Which is least likely? (March 2014)
a. Ependymoma
b. Medulloblastoma
c. Haemangioblastoma
d. Juvenile pilocytic astrocytoma
e. Pleomorphic xanthoastrocytoma
ANSWER: Pleomorphic xanthoastrocytoma – uncommon tumour, 98% occur supratentorially (although this is a tumour of children & young adults 10-30 years)
Which is the most diagnostic finding in glioblastoma on histology? (March 2016)
a. Necrosis
b. Number of mitoses
c. Peripheral extension beyond the margins
d. Extent of perilesional oedema
Features of glioblastoma:
o Increased neovascularity & angiogenesis (microvascular proliferation)
o Causes necrosis & haemorrhage
ANSWER: Necrosis is one of the most important findings in glioblastoma
Mass arising from the septum pellucidum in a 40 year old patient (September 2013, August 2016)
a. Central neurocytoma
b. Meningioma
c. Choroid plexus papilloma
Central neurocytoma
o WHO grade II neuroepithelial tumour
o Heterogenous masses of variable size & enhancement in the lateral ventricle - usually attached to the septum pellucidum
Epidemiology:
- Younger patients (70% 20-40 years) - Rare tumour (<1% of intracranial neoplasms) - No gender predilection
Clinical:
- Present w features of raised ICP
- Short clinical course (over a few months)
• May present abruptly if there is haemorrhage
• May cause sudden death w acute obstruction of the foramen of Munro
Pathology:
- Neuronal differentiation, but histologically similar to oligodendrogliomas
Location:
- Lateral ventricles around the foramen of Munro (50%)
- Both lateral & third ventricle (15%)
- Bilateral lateral ventricles (15%)
- 3rd ventricle in isolation (5%)
ANSWER: Central neurocytoma would be the most likely lesion to arise from the septum pellucidum in a 40 year old patient
Regarding medulloblastoma, which is true? (September 2013)
a. Arises from the roof of the 4th ventricle
b. Most common brain tumour up to age 4
ANSWER: Medulloblastoma arises from the superior vermis, at the roof of the 4th ventricle
Which is false regarding medulloblastoma? (September 2013)
a. High mitotic index
b. Tumour cells form rosettes
c. Round cells with abundant cytoplasm
ANSWER: Medulloblastomas are small round blue cell tumours – they do not have abundant cytoplasm
Which is least likely regarding meningioma? (March 2014)
a. Contains haemorrhage and necrosis
b. Can invade the overlying bone
c. Can appear as an en-plaque meningioma
d. Can exhibit pressure effects on the adjacent brain
ANSWER: Haemorrhage and necrosis are considered characteristics of atypical meningiomas
Which metastasises to dura over intra-axial brain? (March 2015)
a. Breast
b. Lung
c. Prostate
•Primary malignancies which cause dural metastases (most to least common): o Breast cancer o Prostate cancer o Lung cancer o Head & neck cancers o Haematological cancers o Neuroblastoma
Mechanisms by which dural metastases occur:
o Direct extension (from skull metastases)
o Retrograde seeding though the vertebral venous plexus
o Haematogenous
o Lymphatic
ANSWER: Prostate, as breast cancer & lung cancer are more likely to cause metastases in the brain
All of the following metastasize to the brain except: (March 2014)
a. Lung
b. RCC
c. Breast
d. Prostate
e. Melanoma
ANSWER: Prostate – rare to the cranium but typically causes dural metastases. Renal cell metastases to the brain are uncommon (8%).
Which is most likely to cause haemorrhagic brain metastases? (March 2016)
a. Choriocarcinoma
Causes of haemorrhagic brain metastases: o Melanoma o Renal cell carcinoma o Choriocarcinoma o Thyroid carcinoma o Breast cancer o Bronchogenic carcinoma
All of the following are associated with NF1 except: (March 2014)
a. Acoustic schwannoma
b. Kyphoscoliosis
c. Café au lait spots
d. Optic glioma
ANSWER: Acoustic schwannoma – this is assoc w NF2
What is not associated with NF1? (August 2016)
a. Multiple meningiomas
Features of NF1: CNS: - FASI (focal areas of signal intensity) in the deep white matter & BG or corpus callosum. Increased T2 / FLAIR high signal w no contrast enhancement - Optic nerve glioma - Progressive sphenoid wing dysplasia - Lambdoid suture defects - Dural calcification at the vertex - Moya moya (rare) - Buphthalmos – enlarged globe due to increased intraocular pressure w/out deformation or intrinsic mass
Cutaneous:
- Cutaneous or subcutaneous neurofibromas: benign peripheral nerve sheath tumours
Skeletal:
- Kyphoscoliosis
- Posterior vertebral scalloping
- Hypoplastic posterior elements
- Enlarged neural foramina
- Ribbon rib deformity, notching & dysplasia
- Dural ectasia
- Tibial dysplasias - bowing & pseudoarthroses
- Severe bowing & gracile bones
- Multiple non-ossifying fibromas
- Limb hemihypertrophy
Thoracic:
- Mediastinal masses:
• Neurofibroma
• Lateral thoracic meningocoele - Usually on the convex side of the scoliosis
• Extra-adrenal pheochromocytoma
- Lung parenchymal disease (20%)
• Diffuse interstitial fibrosis (lower zone)
• Bullae formation (upper zone)
• Secondary pulmonary arterial HTN & cor pulmonale
Vascular
- Aneurysms, AV malformations
- Renal artery stenosis
- Coarctation of the aorta
Features of NF2:
o Ependymomas
o Multiple meningiomas
o Schwannomas - Bilateral acoustic Schwannomas
ANSWER: Multiple meningiomas are not typical of NF1, however they are seen in NF2
What is associated with rhabdomyomas? (March 2015)
a. Angiomyolipomas
b. Rhabdomyosarcoma
Tuberous sclerosis Major features: o Facial angiofibroma or forehead plaque o Non-traumatic ungula or periungual fibroma o Hypomelanotic macules o Shagreen patch o Multiple retinal hamartomas o Cortical tubers o Subependymal nodules/hamartomas o Subependymal giant cell astrocytoma o Cardiac rhabdomyoma o Lymphangiomyomatosis o Renal angiomyolipomas
Minor features: o Dental pits (multiple & randomly distributed) o Rectal polyps (hamartomatous) o Bone cysts o Cerebral white matter migration lines o Gingival fibromas o Non renal hamartomas o Retinal achromatic skin patch o ‘Confetti’ skin lesions o Multiple renal cysts
Other: o CNS: Cerebellar atrophy Infarcts due to occlusive vascular disorders Cerebral aneurysms Corpus callosum agenesis Chiari malformations Arachnoid cysts Chordoma o Abdominal: Renal Ca & oncocytomas (same population incidence but occur at a younger age) Retroperitoneal lymphangiomyomatosis (may be complicated by chylous ascites)
ANSWER: Angiomyolipomas as part of the tuberous sclerosis complex
Which is most linked to tuberous sclerosis? (August 2014, March 2016)
a. Angiomyolipoma
b. Clear cell carcinoma
ANSWER: AMLs are most strongly linked w TS. RCC rates are similar to the b/g population, but occur at a younger age.
Which is most likely to affect the lungs and the kidneys? (August 2014)
a. Diabetes
b. PAN
c. Tuberous sclerosis
ANSWER: TS affects the lungs (LAM) & kidneys (AML)
Which is not a feature of NF2? (August 2014, March 2017)
a. Ependymoma
b. Meningioma
c. Schwannoma
d. Optic nerve glioma
e. Marked choroid plexus calcification
ANSWER: Optic nerve glioma – assoc w NF1
Which is false regarding VHL? (September 2013)
a. Associated with papillary RCC
f. Associated with clear cell RCC
g. Associated with renal haemangioblastoma
h. Associated with cerebellar haemangioblastoma
ANSWER: VHL is assoc w retinal not renal haemangioblastoma; clear cell RCC is the most common assoc subtype
Which is true regarding neurocutaneous syndromes? (September 2013)
a. Hereditary haemorrhagic telangiectasia is assoc w mucosal telangectasias & an increased incidence of AVMs in the brain & lungs
b. Tuberous sclerosis is assoc w subependymomas
c. Sturge-Weber is assoc w cortical malformations
ANSWER: HHT is associated with mucosal telangectasis and increased incidence of AVMs in the brain & lungs
(TS is assoc w supependymal nodules / hamartomas / SEGA, not subependymoma)
Which is true regarding spinal cord tumours in adults? (September 2013)
a. Ependymomas & haemangioblastomas are most common
b. The most common intradural extramedullary lesions is a meningioma
c. The most common intradural extramedullary lesions is lymphoma
d. Myxofibrillary ependymoma arises from the cervical spine
Intramedullary spinal cord lesions:
o Glial neoplasms (90%)
- Spinal ependymoma (60%) - Most common tumour overall, seen in adults & paediatric patients. Most common neoplasm in adults. 2nd most common in children
- Spinal astrocytoma (33%) - 2nd most common SC tumour. Most common neoplasm in children
- Spinal ganglioglioma (1%)
o Non glial neoplasms Highly vascular lesions: • Spinal haemangioblastoma • Spinal paraganglioma Other: • Metastases • Primary lymphoma • Primitive neuroectodermal tumour • Solitary fibrous tumour
o Intramedullary benign lesions
- Spinal canal epidermoid - Spinal canal lipoma
Intradural extramedullary spinal tumours:
o Spinal meningioma - 2nd most common – 25%
o Spinal nerve sheath tumours:
- Schwannoma - Most common – 30%
- Neurofibroma
o Spinal leptomeningeal metastases
Lesions of the cauda equina & filum terminale:
o Myxopapillary ependymoma
o Spinal nerve sheath tumours: Schwannoma & Neurofibroma
o Spinal paraganglioma
o Spinal lymphoma or leukaemia
o Metastases
ANSWER: Ependymomas are the most common intramedullary SC lesions (60% of glial neoplasms). Haemangioblastomas are less common, but probably the most common non-glial SC lesion.
Meningiomas are the 2nd most common extramedullary intradural lesion, behind schwannoma
Which process does not affect the corpus callosum? (March 2016)
a. Hypoxia
b. Marchiafava Bignami
c. Lymphoma
d. Glioblastoma
e. Multiple sclerosis
DDx of corpus callosal lesions: o Neoplasms: Primary CNS lymphoma Butterfly glioma (glioblastoma) Anaplastic astrocytoma Gliomatosis cerebri Callosal oligodendroglioma o Demyelination & white matter disease: Multiple sclerosis & NMO ADEM PML Metachromatic leukodystrophy X-linked adrenoleukodystrophy Marchiafava-Bignami disease o DAI o Enlarged perivascular spaces o Transient lesion of the splenium o Corpus callosum impingement syndrome o AVM o Tubonodular pericallosal lipoma (assoc w CC agenesis) o Susac syndrome o Infarction
Marchiafava-Bignami:
o Rare disorder of the CNS
o Seen in the setting of ETOH & malnutrition - Middle aged men most commonly affected
o Usually involves the CC: necrosis & demyelination
Pathology:
Deficiency of all eight B group vitamins
Striking myelin loss & axonal degeneration
Imaging:
- Begins in the body of the CC
- Later involves the genu & splenium
- Involves the central layers w sparing of the ventral & dorsal extremities (sandwich sign)
- Demonstrates diffusion restriction
Susac syndrome:
o AKA SICRET syndrome: small infarctions of cochlear, retinal & encephalic tissue
Epidemiology: Rare, Affects middle age women
Clinical: Triad: • Acute or subacute encephalopathy • Bilateral sensorineural hearing loss • Branch retinal artery occlusions - May present at the same time or over a period of 1-2 years w fluctuation
Pathology:
Thought to be autoimmune
Endotheliopathy affecting small vessels w subsequent embolization
Anti-endothelial cell antibodies are thought to have a role (but are not specific)
Imaging features:
- Multiple small white matter lesions w a predilection for the CC
- Corpus callosal lesions:
• Involve the central fibres of the body & splenium w sparing of the peripheral
• Lesions are small (3-7mm) & resemble ‘snowballs’. Best seen on sagittal
• The roof of the CC is frequently involved, gives the appearance of ‘icicles’ hanging from the roof
Other areas which are involved: periventricular white matter, centrum semiovale, cerebellum, brainstem & middle cerebellar peduncles
ANSWER: Hypoxia is less likely to involve the corpus callosum. Machiafava-Bignami typically involves the corpus callosum
