Introduction:
Cerebral necrosis or radiation-induced brain necrosis (RBN) is a serious complication of intracranial tumors after radiotherapy. Radiotherapy is considered an important treatment protocol to treat brain tumors, and its efficacy has also been confirmed over the years. However, radiation therapy increases the risk of nerve damage, such as focal cerebral necrosis, neurocognitive dysfunction, cerebrovascular disease, myelopathy, and brachial plexus neuropathy.
Therefore, the development of radiation-induced brain necrosis (RBN) depends on the total radiation dose, the fraction size, and the brain volume. Usually, the higher the total radiation dose, split dose, and brain volume, the higher the incidence of RBN. They typically present as headaches, insanity, dizziness, memory loss, personality changes, and seizures. These symptoms may severely affect the quality of life of patients.
Radiation necrosis can occur in three phases:
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Radiation therapy for head and neck malignancy.
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Stereotactic radiation therapy for brain metastasis.
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Radiation therapy for primary brain tumors.
Appropriate information about the radiation treatment plan, amount of brain tissue in the radiation port, type of radiation, the site of the primary malignancy, and the duration of time elapsed since radiotherapy is important to distinguish whether the imaging abnormality is caused by radiation necrosis or recurrent tumor.
Although conventional imaging techniques such as magnetic resonance imaging (MRI) reveal overlapping features of radiation necrosis with recurrent tumors, overlapping features can be seen under histopathological studies as they show tumors mixed with radiation necrosis. Therefore, advanced imaging techniques like diffusion tensor imaging, perfusion MR imaging, MR spectroscopy, and positron emission tomography are quite effective in comparing radiation necrosis from recurrent tumors.
What Is the Pathophysiology of Radiation-Induced Brain Necrosis?
It usually starts with a radiation-induced vascular injury within the first 24 hours of radiation. A cerebral parenchymal injury follows this. Next, the ionizing radiation typically induces reactive oxygen species in tumor cells, causing irreversible DNA (deoxyribonucleic acid) damage. As a result, the DNA repair pathways are activated, causing the cell cycle to arrest and irreversible apoptosis of DNA to take place. Radiation may also interact with cytoplasmic membranes, destroying the endothelial cells and leading to ceramide-induced apoptosis. This will trigger a series of events that will lead to cellular swelling and necrosis, an increase in the production of reactive oxygen species, and the transmission of inflammatory responses such as cytokines and chemokines.
The formation of fibrin-platelet thrombus and fibrinoid necrosis destroys the blood-brain barrier, causing cerebral edema. In addition, radiation therapy can directly destroy the brain vessels' glial cells and endothelial cells, leading to hyalinization and demyelination of the blood vessels, followed by inflammation, ischemia, and delayed radiation necrosis. Usually, after the exposure of the brain to radiation, an inflammatory response takes place. Within a few hours of radiation, the microglia are activated, the shape of the cells is altered, and the damaged nerve transcription factors are activated along with the production of proinflammatory mediators, leading to damage to the central nervous system.
What Are the Signs and Symptoms of Cerebral Necrosis?
The clinical features of cerebral necrosis vary depending on the severity of the disease and the site involved. Patients usually do not have any symptoms or are asymptomatic; sometimes, a few patients may complain of focal neurological deficits, raised intracranial pressure, or cognitive impairment.
What Are the Investigation to Be Carried Out?
Well-detailed history taking of the patient would reveal the history of radiotherapy in the head and neck region. RBN can appear after radiotherapy for benign and, more commonly, malignant tumors, which may be associated with a high radiation dose. It usually occurs after six months to one year of radiotherapy. Patients who require multiple radiotherapies are more susceptible to RBN. Although pathological biopsy is the gold standard diagnostic tool, due to the invasiveness of biopsy and the large sampling error, RBN needs to be correlated with the patient's medical history, symptoms, and imaging examinations to confirm the diagnosis.
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MR Perfusion Scan: It helps in comparing tumor recurrence from tumor necrosis. In tumor necrosis, areas of complex blood vessels with increased permeability around the tumor site appear as areas of hyperperfusion. In contrast to this, cerebral necrosis shows areas of decreased perfusion due to vascular endothelial damage and coagulative necrosis.
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MR Spectroscopy (MRS): It is used to grade the tumors. It comprises N-acetyl aspartate (NAA), choline, creatine, and lactate. A typical malignant tumor has low levels of NAA and creatine, high levels of choline and lactate, and different lipid compositions. An MRS has proven beneficial in differentiating cerebral necrosis and tumor recurrence. However, an early investigation may show low spatial resolution and the inability to accurately classify tumor recurrence and cerebral necrosis.
What Is the Treatment of Cerebral Necrosis?
The symptoms, disease status, and development of suspected lesions on diagnostic imaging are considered the most significant factors in managing cerebral necrosis. Asymptomatic and small lesions require an observational wait strategy, with continuous clinical follow-up and diagnostic imaging.
Close imaging follow-up is usually recommended at short intervals at the beginning of the treatment. If the lesion size reduces, then the frequency of follow-up can be reduced as per the specific cases. Symptomatic brain necrosis involves treating the underlying causes either by surgical interventions, glucocorticoids such as Dexamethasone, or anticoagulants are recommended. With a better understanding of the disease, various treatment strategies using hyperbaric oxygen therapy and high-dose vitamins have proven beneficial.
Conclusion:
Identifying the underlying cause of the lesion is of utmost importance in neuro-oncology for both diagnoses and treatment planning. Though biopsy is considered the gold standard diagnostic tool for differentiating tumor recurrence and cerebral necrosis, it involves risk factors at the time of surgery.
Therefore, there is a need for non-invasive methods to differentiate between the two lesions. This will reduce the risk of unnecessary intervention and improve the quality of life of the patient and chances of survival. In addition, advanced imaging techniques like diffusion tensor imaging, perfusion MR imaging, MR spectroscopy, and positron emission tomography are quite effective in comparing radiation necrosis from recurrent tumors.
