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Metastatic Brain Disease

 Metastatic Brain Disease


  • Introduction
  • Epidemiology
  • Surgical Anatomy
  • Pathology
  • Management
  • Future trends
  • Conclusion


  • Metastatic brain disease is one of the most undesirable effect of systemic cancer
  • It overshadows primary brain tumour in frequency
  • It affects both the brain parenchyma and leptomeninges
  • Intense vigilance is necessary for early diagnosis
  • Surgery and radiotherapy is the cornerstone for treatment
  • Preventive measures presently are ineffective


  • Metastatic brain diseases are more common than primary brain diseases with 7-14 new cases recorded per 100000 in the US
  • 15-30% of patients with Cancer develop cerebral metastasis
  • In patients with no History of cancer, cerebral metastasis was the presenting symptom in 15% of patients• 43-60% have abnormal chest x-ray findings of canon ball metastasis
  • 9% have cerebral metastasis as the the only detectable site
  • There are more common in adults than children
  • The most common primary tumours responsible for brain metastases are
    • Lung cancers 19.9%
    • Melanoma 6.9%
    • Renal Cancer 6.5%
    • Breast Cancer 5.1%.
    • Colorectal 1.8%
  • Increasing incidence is due to Increasing survival of Cancer patients
  • Enhanced diagnostic modalities
  • Inability of most chemotherapeutic agents to cross the BBB, making it a sanctuary for tumour growth

Relevant anatomy

  • The brain is divided into
    • Forebrain
    • Midbrain
    • Hind brain
  • Covered by the meninges
  • Circle of willis formed by branches of the vertebral artery and internacarotids
  • Support cells microglia and astrocytes


  • Haematogenous
  • Lymphatic
  • Csf
  • Most have involvement of the lungs
  • High blood flow to the brain ( 15-20%)
  • Certain primaries find the brain an appropriate place for metastatic colonization
  • Renal, colon and breast carcinomas generally produce single metastases
  • Whereas malignant melanoma and lung cancers generally produce multiple secondary lesions
  • The site and distribution of brain metastases is also determined by the size of the region and its vasculature
  • 85% of Brain Mets are therefore found in the cerebral hemispheres in the watershed area between the middle and posterior cerebral arteries
  • 10-15% are found in the cerebellum and only 3% in the brain stem
  • While breast cancers tend to metastasize to the posterior pituitary
  • Renal-cell, gastrointestinal and pelvic cancers tend to metastasize to the infratentorial area
  • Breast ca to the posterior pituitary

Biology of brain metastases

  • Paget in 1889 said that
    • The seeds of a plant are carried in all directions; but they can only live and grow if they fall on congenial soil
    • The properties of cancer cells and their potential target organs are factors that potentiate metastatic cancer cell growth
    • Arrest of cancer cell in brain capillary
    • Mediated by integrins
    • Extravasation across the BBB into the brain parenchyma
    • HBEGF,COX2 AND ST6GALNAC5 genes mediates this
    • They grow perivascular or recruit new blood vessels via angiogenesis
    • Astrocytes provide invasion advantages to the disseminated tumour
    • Produce survival genes for the tumour GSTA5, BCL2L1 and TWIST1, further increase its resistance to chemotherapy
    • Growth of the tumour is also critically dependent on angiogenesis
    • The angiogenesis in this case is disordered with defective endothelial cells, pericytes covering and basement membrane
    • This restricts O2 delivery leading to intramural hypoxia
    • This also limits chemo and radiotherapeutic agents from reaching the tumour hence enabling a sanctuary for it
    • Factors that will improve tissue perfusion will enhance treatment of this tumour

Clinical features

  • Headache
  • Change in mental state
  • Motor weakness
  • Sensory disturbances
  • Nausea and or vomitting
  • Seizures
  • Ataxia
  • Speech difficulties
  • Coordination abnormalities
  • Neurocognitive test
  • Mental state examination is essential before commencement of therapy


  • Baseline

    • fbc,
    • blood chemistry (suecr, LFT,),
    • CXRAY,
    • Abdominopelvic USS

  • Diagnostic investigation:

    • Contrast enhanced CT or MRI

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