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
Epidemiology
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
Pathophysiology
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
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