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
