MRI is particularly useful as it can differentiate between cytotoxic and vasogenic edema, guiding future treatment decisions. Intracranial pressure monitoring
Intracranial pressure (ICP) and its management is a fundamental concept in traumatic brain injury (TBI). The Brain Trauma Foundation guidelines recommend ICP monitoring in individuals with TBI that have decreased Glasgow Coma Scale (GCS) scores, abnormal CT scans, or additional risk factors such as older age and elevated blood pressure. However, no such guidelines exist for ICP monitoring in other brain injuries such as ischemic stroke, intracerebral hemorrhage, cerebral neoplasm.Clinical researches have recommended ICP and cerebral perfusion pressure (CPP) monitoring in any persons with cerebral injury who are at risk of elevated intracranial pressure based on clinical and neuroimaging features. Early monitoring can be used to guide medical and surgical decision making and to detect potentially life-threatening brain herniation. There was however, conflicting evidence on the threshold values of ICP that indicated the need for intervention. Researches also recommend that medical decisions should be tailored to the specific diagnosis (e.g. subarachnoid hemorrhage, TBI, encephalitis) and that ICP elevation should be used in conjunction with clinical and neuroimaging and not as an isolated prognostic marker. Treatment
The primary goal in cerebral edema is to optimize and regulate cerebral perfusion, oxygenation, and venous drainage, decrease cerebral metabolic demands, and to stabilize the osmolality pressure gradient between the brain and the surrounding vasculature. As cerebral edema is linked to increased intracranial pressure (ICP), many of the therapies will focus on ICP.
Talazoparib, sold under the brand name Talzenna, is an orally available poly ADP ribose polymerase (PARP) inhibitor developed by Pfizer for the treatment of advanced breast cancer with germline BRCA mutations. Talazoparib is similar to the first in class PARP inhibitor, olaparib. It was approved in October 2018, in the United States and June 2019, in the European Union for germline BRCA-mutated, HER2-negative locally advanced or metastatic breast cancer. Side effects
The most serious side effects in studies were related to the blood forming system and included anaemia (low red blood cell count), neutropenia (low neutrophil blood cell count) and thrombocytopenia (low platelet count). Serious forms of these conditions (grade 3 to 4) occurred in 39%, 21% and 15% of patients, respectively. Other adverse effects such as headache, nausea, hair loss and fatigue were mostly mild. Interactions
Combination with drugs that inhibit P-glycoprotein or BCRP may increase talazoparib concentrations in the body. Mechanism of action
Talazoparib acts as an inhibitor of poly ADP ribose polymerase (PARP) which aids in single strand DNA repair. Cells that have BRCA1/2 mutations are susceptible to the cytotoxic effects of PARP inhibitors because of an accumulation of DNA damage. Talazoparib is theorized to have a higher potency than olaparib due to the additional mechanism of action called PARP trapping. PARP trapping is the mechanism of action where the PARP molecule is trapped on the DNA, which interferes with the cells ability to replicate. Talazoparib is found to be ~100 fold more efficient in PARP trapping than olaparib.