8.3.2 CNS Tumours Flashcards
What are the two types of CNS tumours?
Primary
- Gliomas
- Parenchymal
- Meningeal
- Neuronal
- Poorly differentiated- medulloblastoma
Secondary
- Metastatic- paraneoplastic
What are some examples of gliomas?
Think of what glial cells actually are
-Astrocytic tumours
-Oligodendrogliomas
-Ependyomas
-Colloid cysts of 3rd ventricle
What are the types of parenchymals tumours?
CNS lymphomas
Germ cell
What are meningeal tumours called?
Meningiomas
What are the different types of neuronal tumours?
Ganglion cell tumours
Neuroblastomas
What are gliomas?
Malignant tumours
Graded 1-5
Astrocytic tumours
- Most common is astrocytic, low to high grade, 80%
- Glioblastoma multiforme- grade 4-5
Oligodendrogliomas
- 20% gliomas, grade 2-4
Ependymoma
- Ventricular system
- Often disseminated into CSF
What are lymphomas?
Diffuse, large B cell lymphomas
Associated with EBV
What are germ cell tumours?
Midline tumours, pineal and suprasellar
e.g. germinoma
Where do medulloblastomas occur?
Cerebellum
20% children
Radiosensitive
What are meningiomas?
Benign
Derived from arachnoid meningothelial cells
Can compress structures
How can infection enter into the CNS?
Direct- Air sinuses, skull fractures
Haematogenous- Arterial blood, venous sinuses
Iatrogenic- LP, surgery
Peripheral nerve- HZV, viruses
What is affected by infections entering the CNS?
Meninges
Aggregates of acute inflammation
Brain parenchyma
What is meningitis?
Inflammation of leptomeninges
What are the different types of meningitis?
Acute pyogenic- Bacterial
Aseptic- Viral, immunocompromised
Chronic- myco tuberculosis- fungi
Carcinomatosis- spread of cancer
May be due to septicaemia
How does meningitis present?
Headache
Photophobia
Irritability
Altered consciousness
Stiff neck- meningeal irritation
Focal neurological impairment
What investigations are done for meningitis?
CT scan
Lumbar puncture
What are the complications of meningitis?
Cerebral oedema
Cerebral infarction
Cerebral abscess / empyema
Epilepsy
Meningoencephalitis
Septicaemia
What infective organisms cause meningitis at each age?
Infants
- Escherichia Coli
- Group B streptococci
Young adults
- Neisseria meningitidis
Older adults
- Streptococcus pneumoniae
- Listeria monocytogenes
Chronic meningitis
- Mycobacterium tuberculosis
What organisms causes a cerebral abscess?
Streptococci or staphylococci
What organisms cause empyema?
Polymicrobial (staphylococci, anaerobic gram -ve)
What is encephalitis?
Infection of the brain parencyma
What are some features of encephalitis?
Usually viral
Neurone death by viruses
Prominent lymphocytes
Give some examples of viruses causing encephalitis and what lobe they affect
Herpes Zoster- Temporal lobe
Polio
Spinal cord motor neurones
Rabies
Brainstem
What viruses can cause encephalitic syndromes?
Herpes simplex virus, HSV-1 and HSV-2
CMV
HIV
What are prion diseases?
Abnormal cellular protein accumulations which lead to cell injury in and out of the cell:
- Neurone cell death
- Synapse loss
- Microvacuolations
- Lack of inflammation
Why are prion diseases infective?
Causes abnormal protein aggregates to accumulate in local cells
What can cause prion diseases?
Sporadic
Familial
Iatrogenic
Ingested (think of House episode with the water)
What are the different types of prion disease?
- Creutzfeldt- Jakob Disease and variant CJD
- Scrapies (sheep)
- Bovine spongiform encephalopathy (Mad Cow disease)
What happens to proteins in prion disease?
Normal brain proteins are rich in alpha helices
Initiation
Prion disease ingested. inoculated or sporadic, this causes conformational change to beta pleated sheet
Propagation
Abnormal proteins cause surrounding proteins to undergo conformational change from alpha helices to beta pleated sheets
Aggregation
Abnormal proteins aggregate forming amyloid plaques and spongiform brain
What are the features of Creutzfeld Jakob Disease?
- Normally sporadic (familial form)
- 1 per million very rare
- Rapidly progressive dementing illness
- Subtle changes in memory
- Cerebellar ataxia
- Global dementia
- Definitive diagnosis- post mortem
- Often brain looks normal, may have atrophy or ventricular enlargement
What are the features of variant Creutzfeld Jakob Disease?
- Affects young adults
- Slower progression
- Starts with behavioural issues
- Exposure due to cattle- e.g. meat and blood transfusions
- Prolonged incubation, 15 years
What causes neurodegenerative diseases?
Loss of neurones
Accumulation of protein aggregates
What happens in neurodegenerative diseases affecting the hippocampus and cerebral cortices?
Changes in:
- Cognitive
- Memory
- Behaviour
- Language
What happens in neurodegenerative diseases affecting the Basal ganglia?
Movement disorders, hypo/hyperkinetic
What happens in neurodegenerative diseases affecting the cerebellum?
Ataxias, motor neurones can also be hit
Who is affected by Alzheimer’s disease?
3% of 65-74 year olds, increases with age
Sporadic 90% of the time
Can be familial which causes earlier onset, 5-10%
What happens in Alzheimer’s?
Alpha beta plaques and neurofibrillary tangles (tau) form
This accumulation causes neuronal damage, this leads to loss of neurones
Loss of neurones causes cortical atrophy and shrunken brain
Affects frontal, temporal and parietal lobes
How do plaques and tangles form?
Amyloidogenic pathway
- Transmembrane protein on chromosome 21 cleaved to alpha beta monomer by beta and and gamma secretase
- Alpha beta monomers clump together forming oligomers, these then aggregate forming fibrils which then form tangles
- Tau aggregates are formed by alpha beta oligomers becoming hyperphosphorylated, this causes neuronal damage
Non-amyloidogenic pathway
- Alpha and gamma secretase cleave
Why are people with Down syndrome at increased risk of Alzheimer’s disease?
Protein which causes Alzheimer’s is found on chromosome 21
In Down syndrome, there are 3 chromosome 21s, therefore more likely to have plaque and tangle formation
What are the signs and symptoms of Alzheimer’s?
Impaired memory
Impaired intellectual function
Altered mood and behaviour
Disorientated
What causes Parkinson’s disease?
Loss of dopaminergic neurones in the substantia nigra pars compacta
Lewy body involvement (alpha synuclein)
What are the symptoms of Parkinson’s?
Sometimes TRAPPED D*ck Means Femoral Hernia
Shuffling gait
Tremor
Rigidity
Akinesia
Pill-rolling tremor
Postural instability
Expressive aphasia
Dementia
Depression
Micrographia
Facial weakness
Hypokinesia
What causes Huntington’s?
Autosomal dominant condition
Increased CAG repeats
Mutant protein broken down to aggregates which causes damage
Loss of inhibitory neuronal projection to corpus striatum
What are the signs of Huntington’s?
CDCD
Chorea
Distonia
Co-ordination loss
Decline in cognition
