Neurological tumours Flashcards
Epidemiology of primary brain tumours
10 in 100,000
Aetiology of brain tumours
- Definitive cause is often unknown
- Various inherited conditions increase risk of intracranial tumour development
- Environmental: immunosuppression, HIV
- Brain irradiation e.g. used to treat childhood leukaemia, increases risk of tumours, especially meningiomas
Pathogenesis of brain tumours
- Tumours are either benign or malignant but important to note that even benign IC tumours can cause severe destruction of surrounding structures
- Malignant IC tumours rarely metastasise outside the nervous system
Clinical features of brain tumours
- Raised ICP, herniation
- Acute/ chronic focal neurological deficits
- Seizures
- Headaches
- Changes in mental status
- Hydrocephalus
Clinical features of IC tumours based on location
- Frontal lobe: contralateral weakness of arm, leg or face, personality change, expressive speech dysfunction if dominant hemisphere affected
- Parietal lobe: contralateral sensory deficit in face, arm or leg, visual field defect
- Temporal lobe: receptive speech dysfunction (if dominant hemisphere affected), visual field defect
- Occipital lobe: visual field defect, cortical blindness
- Sellar regional cavernous sinus syndrome (CNIII - VI deficits), endocrine dysfunction, optic chiasm compression
- Brain stem: cranial nerve lesion, decreased consciousness
- Cerebellum: dysdiadochokinesia, ataxia, intention tremor, nystagmus
Classic features of brain tumour headaches
- Worse in morning
- Exacerbated by coughing or straining
- N&V
Effects of benign tumours
- Blindness due to optic nerve compression
- Paralysis by pressing on primary motor cortex
- Life-threatening hydrocephalus by obstructing ventricular system
Diagnosis of intracranial tumours
- Imaging + biopsy if needed
- Plain CT: confirms presence of space occupying lesion
- Subsequent contrast enhanced CT shows tumours as ring enhancing
- Diffusion weighted MRI can better differentiate between a tumour and an abscess
What are gliomas?
- Tumours that originate from neuroepithelial glial cells
- >70% primary brain tumours are gliomas, mainly astrocytomas
- Glioblastoma multiforme is the most common high-grade tumour
Types of gliomas
Low grade: WHO grade 1&2
- Pilocytic astrocytomas (grade 1) are well-circumscribed low grade gliomas, they grow slowly and can be cured by surgical resection. They arise in the optic pathway or hypothalamus in association with neurofibromatosis type 1
Grade 2 tumours
- E.g. diffuse astrocytomas often lack a margin between tumour and non-tumour tissue, making resection more difficult. Grade 2 tumours are more likely to evolve into higher grade tumours
- Ependymal and oligodendrocytic tumours are less common than astrocytomas but investigation and management are similar
High grade: WHO grade 3&4
- Glioblastoma multiforme is grade 4
Clinical features of gliomas
- Present similarly to other IC tumours
- Seizures, as a presentation, are more common with lower grade tumours
Management of gliomas
- Symptomatic grade 1 gliomas are surgically removed, location permitting
- Grade 2: watch and wait with serial imaging and clinical assessment, surgery, xRT, chemo, a combination of surgery, xRT and chemo
- No study has shown one is better than the other
- Partial removal of the tumour can also be beneficial
- Important to image the tumour to find areas that appear to be high grade so these areas can be biopsied - heterogeneity of tumours…
What is glioblastoma multiforme?
- Grade 4 glioma of astrocyte origin
- Most common malignant primary brain tumour (12-15% of all primary brain tumours)
- Most commonly presents in patients aged 50-60
- Generally arise in the cerebrum but can occur anywhere
Types and causes of glioblastoma multiforme
Glioblastoma multiforme can be primary or secondary
- Primary: >90% cases, de novo tumours in elderly patients with no evidence of a low grade lesion
- Secondary: younger patients, usually progressing from a lower-grade tumour
The two types are histologically the same but genetically different, secondary tumours carry a better prognosis
Clinical features of glioblastoma multiforme
- Develop rapidly
- Most commonly raised ICP and focal neurological deficits
Management of glioblastoma multiforme
- Tumours are commonly diffusely infiltrative without a clear margin
- Surgical resection as a cure is almost impossible
- Best option is to resect as much as possible and follow up with chemo and xRT
Prognosis of glioblastoma multiforme
- Median survival is <18months
- <3% alive at 5 years
What are meningiomas?
- Primary tumours that probably originate from arachnoid mater
- Can develop at any site where meninges are
- Can grow near dural sinuses making removal difficult due to high risk of haemorrhage and infarction
Epidemiology of meningiomas
- 15% primary brain tumours are meningiomas
- M:F 1:2
- Mid 40s peak incidence
Cause of meningiomas
Unknown but radiation association esp. if exposure in childhood
Management of meningiomas
Determined by
- Patient age
- Tumour size
- Tumour location
- Clinical features/ presentation
- Meningiomas are frequently benign and low grade and can be resected
- High grade forms e.g. anaplastic meningiomas usually require post-op xRT to reduce risk of recurrence
- Monitoring for low grade tumours that are small and not associated with oedema
- Can cause seizures and these can be managed with AEDs
What are nerve sheath tumours?
- Rare, arise from nerves or nerve sheaths
- Can occur in any cranial, spinal or peripheral nerve
Types of nerve sheath tumours
Schwannomas: arise from Schwann cells - the most common intracranial being vestibular schwannomas
- If a patient has bilateral schwannomas they have neurofibromatosis type 2
Neurofibromas: originate from Schwann cells and other nerve components
Clinical features of nerve sheath tumours
Symptoms or signs related to dysfunction in a specific nerve
Can also cause compression of local structures
- Brain stem or other cranial nerves
- Vestibular schwannoma may compress cranial nerve VII causing facial weakness or the cochlear part of cranial nerve VIII causing deafness and tinnitus
Management of nerve sheath tumours
- Watch and wait
- Surgery
- Stereotactic radiosurgery: fewer, high dose, highly localised treatments
What is neurofibromatosis?
- One of the neurocutaneous syndromes
- Hereditary disorders characterised by multi-organ malformations and tumours
Epidemiology of neurofibromatosis
- NFT1: 1 in 2500
- NFT2: 1 in 50,000
Aetiology of neurofibromatosis
- Both types are AD
- Overgrowth of embryonic ectodermal tissue
- The result is a loss of tumour suppressor gene function
- Tumours are usually benign (<1% malignant)
Clinical features of neurofibromatosis
NFT1
- Skin: café-au-lait spots, freckling, neurofibromas
- CNS: intracranial tumours, intraspinal tumours, epilepsy
- PNS: peripheral nerve neurofibroma
- Solid organs/ blood: medullary thyroid cancer, leukaemia
- Meningiomas
- Bones: scoliosis, bone hypertrophy
- 5% of patients with NFT1: sarcomatous malignant changes in a neurofibroma
- Classical feature in NFT2: bilateral vestibular schwannomas, skeletal manifestations often absent
NFT2
- CNS: bilateral acoustic neuromas/vestibular schwannomas (hallmark), neuromas, gliomas
- Eyes: cataracts (juvenile posterior subscapular)
- Skin: rare to get café-au-lait spots
Diagnostic criteria for neurofibromatosis
Strict diagnostic criteria for both types, family history, physical examination, MRI are essential
Diagnosed if 2+ present:
- 6+ café au lait spots
- 2+ nodular neurofibromas
- Freckles on axilla or inguinal region
- 2+ Lisch nodules (eyes)
- 1st dgeree relative w/ NFT1
- Distinctive bone lesion e.g. sphenoid wing dysplasia
Presence of bilateral acoustic neuromas is diagnostic of NFT2
Management of neurofibromatosis
- Managed by MDT of geneticists, neuro, plastics and PT
- Symptomatic treatment: anticonvulsants for epilepsy
- Intracranial and intraspinal tumours may need removing surgically if associated with compressive symptoms
Familial screening and genetic counselling important
What is tuberous sclerosis complex?
- Neurocutaneous condition
- Less common than NF
- 1 in 30,000
Aetiology of tuberous sclerosis
AD inheritance
- High rate of sporadic mutation
Due to mutations in hamartin/ tuberin tumour suppressor genes
- Results in abnormal cell signalling, growth and migration
Clinical features of tuberous sclerosis
- Ectodermal tumours affecting skin, nervous system, solid organs and bone
- Classic triad (Vogt triad) only occurs in 1/3)
Diagnostic features of tuberous sclerosis
Suspect in patient with seizures + delayed development + facial angiofibromas
Imaging used to assess extent of disease
Major features
- Facial angiofibromas
- Shagreen patches
- Subependymal giant cell astrocytomas
- Cardiac muscle rhabdomyoma
Minor features
- Pitting of teeth
- Bone cysts
- Gingival fibromas
- Multiple renal cysts
Management of tuberous sclerosis
- Seizures controlled with anticonvulsants
- Intracranial lesions can be resected
- mTOR inhibitors for subependymal giant cell astrocytomas
