Brain tumours and neurofibromatosis

Question 1

Epidemiology of brain tumours:

Answer 1

2nd most common paediatric cancer
In adults - usually supratentorial, in children - posterior fossa mainly.
Majority are gliomas (glial cell in origin): Astrocytomas (85%-90%), Oligodendroglioma (5%).
Astrocytoma most common - most malignant grade is called a Glioblastoma Multiforme.

Question 2

Risk factors of primary brain tumour?

Answer 2

More common in affluent groups.
Ionising radiation, vinyl chloride, immunosuppression.
Family history of Neurofibromatosis, tuberous sclerosis, Von-Hippel-Lindau syndrome

Question 3

Types of brain tumour?

Answer 3

1) Glioma - astrocytoma (most common + glioblastoma multiform is most malignant), oligodendroglioma arises from oligodendrocytes and grows slowly over several years, may present with seizures + IDH1 mutation positive.
2) Ependymoma - raising from ependymal cells lining ventricles and spinal cord.
3) Meningioma - most common in older men and women, benign and arises from arachnoid mater and may grow to a large size over years pushing into brain.
4) Neurofibroma - arises from Schwann cells

Tumours be it malignant of benign act as space-occupying lesions within the brain = raised ICP which can eventually result in coning (herniation of brain through foramen magnum leading to compressed brainstem).

Question 4

Clinical presentation of tumours?

Answer 4

4 cardinal presenting symptoms:
1) Symptoms of raised ICP - headache (morning, cough/strain/bending, relieved by vomitting), drowsiness/ALOC, vomitting, papilloedema (swollen optic disc, retinal oedema, loss of crisp optic nerve head margins (take days)). Bradycardia, high BP.
2) Progressive neurological deficit: Depends on area of brain that is affected.
Frontal lobe - Broca’s dysphasia, motor dysfunction (hemiparesis), cognitive decline, personality change, planning.
Temporal lobe - amnesia (memory loss), Wernicke’s dysphasia
Parietal lobe - Hemisensory loss, reduction in 2-point discrimination, dysphasia, asterogenesis
Occipital lobe - Contralateral visual loss
Cerebellum - Dysdiochokinesia, dysmetria, ataxia, speech slurred, hypotonia, intention tremor, nystagmus, gait disturbance.
3) Epilepsy/seizure - More focal/partial seizures - with motor, sensory, and temporal lobe pattern with de ja vu, olfactory aura, and funny feeling in stomach before and during seizure.
4) Lethargy/tiredness due to compression of brainstem.

Question 5

What are other examples of space-occupying lesions?

Answer 5

Aneurysm, hydrocephalus, abscess, haemorrhage

Question 6

Diagnosis of primary brain tumour?

Answer 6

1) CT and MRI - MRI superior for posterior fossa lesions, determine size and location, high grade tumours have irregular edges and high growth rate.
2) Blood tests: FBC, U & E’s, LFT, B12 etc.
3) Biopsy - via skull burr-hole - to determine cancer grade and confirm.
4) LP - is contraindicated when there is any possibility of a mass lesion since withdrawing CSF may provoke immediate coning.

Question 7

Treatment of a primary brain tumour?

Answer 7

1) Surgery to remove mass if possible
2) Radiotherapy if surgery is not possible
3) Chemotherapy for glioma - at same time as surgery and 1st 6 weeks post-op (Temozolomide). Not all tumours are sensitive as they have high MGMT - ensure MGMT is methylated before administering.
4) IV Dexamethasone - improves brain function and reduces oedema and inflammation of tumour
5) IV Carbamazepine - anti-convulsants

Question 8

What are the commonest neoplasms to metastasise to CNS in order?

Answer 8

1) Non small cell lung (most common)
2) Small cell lung
3) Breast
4) Melanoma
5) Renal cell
6) GI (least common)

Question 9

Treatment for secondary brain tumours?

Answer 9

1) Surgery if (<75 yrs)
2) Radiotherapy
3) Chemotherapy
4) Palliative

Question 10

Neurofibromatosis aetiology + epidemiology?

Answer 10

Autosomal dominant condition causing lesions in skin, nervous system and skeleton.
NF1 - Von Recklinghausen’s disease - caused by gene mutation 17 affecting 1 in 4000.
NF2 - much rarer and caused by gene mutation 22 affecting 1 in 100,000, presenting with CNS tumours rather the skin lesions.

Question 11

Difference between NF1 and NF2?

Answer 11

• NF1 presents in childhood, NF2 between 20-40yrs.
• 45% of NF2 presents with hearing problems such as deafness/tinnitus +/- loss of balance/facial weakness.
• NF1 has early onset of cafe-au-lait spots but fewer spots in NF2 (<6).

Question 12

Other conditions with cafe-au-lait spots?

Answer 12

1) Hereditary non-polyposis cancer of the colon.
2) DNA repair syndromes
3) McCune-Albright syndrome

Question 13

NF1 criteria of diagnosis?

Answer 13

> 2 of the following:

1) >6 cafe-au-lait spots - flat, coffee-coloured patches of skin seen in first year of life increasing in number and size with age.
2) >2 neurofibromas - Dermal - small skin nodules after puberty. Nodular - Subcutaneous, firm nodules that can cause parasthesia if compressed.
3) >2 Lisch nodules - nodules of the iris only seen with slit lamp.
4) Pheochromocytoma - tumour of the Adrenal gland causing increased adrenaline/noradrenaline - high BP and sweating
5) First degree relative with NF1
6) Freckling of axilla, groin, sub-mammary in women, neck base present by age 10.

Question 14

NF2 criteria of diagnosis

Answer 14

1 of:
1) Bilateral vestibular Schwannoma (CN8) - acoustic neuroma with hearing loss, vertigo, tinnitus
OR
2) 1st degrees relative with NF2 AND either unilateral vestibular Schwannoma or >1 neurofibroma/glioma

Question 15

Treatment of neurofibromatosis?

Answer 15

1) Neurosurgery to remove tumours
2) Radio/Chemo if location or surgery is difficult
3) Surveillance

Question 16

Complications of neurofibromatosis?

Answer 16

NF1: Mild learning disability, nerve root compression, epilepsy, short stature, macrocephaly, GI bleeding, kyphoscoliosis.

NF2: Schwannomas of other cranial nerves, dorsal nerve roots, peripheral nerves, meningioma.