Non-Invasive Measurement of Absolute Intracranial Pressure in Patients With Mass Effective Brain Tumors

Primary brain tumors in adults are less common than metastatic tumors. The most frequent are glioblastoma multiforme, metastases, anaplastic astrocytoma, meningioma, pituitary tumors and vestibular schwannoma. 70% of the tumors in adults are supratentorial. The most infratentorial tumors are metastases, schwannoma, meningioma, epidermoid, hemangioblastoma, and brainstem glioma. Causes of brain tumors are genetics, radiation, immunosuppression, viruses and chemotherapy.

Clinically patients present with neurological deficits as hemiparesis, cranial nerve deficiency or signs of raised ICP such as headache, nausea, vomitus, vigilance disturbance. After clinical assessment, standard MRI with contrast agent is performed to visualize the size and structure of the tumor, contrast uptake, peritumoral edema (PTE), and other radiological findings. Depending on the tumor, size and location, the further procedure must be defined with either surgical resection, observation, other adjuvant therapies. Mostly, a histological diagnosis is needed to know the tumor biology and set supplementary treatment.

In patients with brain tumors with mass effect and peritumoral edema with consecutive midline shift increased intracranial pressure (ICP) is usually considered. During the expansion of an intracranial mass lesion, there is initially a minimal increase in ICP, but as compensatory capacity is exhausted the volume pressure curve rapidly steepens, and by further expansion of the mass a distinct increase in ICP results.

Supratentorial tumors can produce significant mass effect in the brain. In certain tumor types, especially metastases, high grade gliomas, and meningeomas significant peritumoral edema that lead to elevation of intracranial pressure might be associated. In cases of infratentorial tumors with or without edema earlier clinical decompensation with hydrocephalus, increased ICP and downward herniation are more often due to reduced space within the posterior fossa. Within the closed bony cranium, increase of volume, such as tumor with associated edema or hemorrhage, ischemia, occlusion of venous perfusion or hydrocephalus lead to an increase of ICP and secondary injury to the normal brain. PTE is caused by vasogenic edema in particular, but also cytotoxic edema, tumor-related-pressure, arterial blood supply, venous congestion and secretion of angiogenic factors such as vascular endothelial growth factor (VEGF). VEGF, Aquaporin-4 (AQP4), cyclooxygenase-2 (COX- 2), and nitric oxide (NO) induce dysfunction of tight junction proteins playing an important role in the formation of edema. Cerebral edema induced by brain tumor is characterized by an increase in the permeability of brain capillary endothelial cells and an increase in the brain water content. Peritumoral vasogenic edema as a result of blood-brain-barrier dysfunction within the tumor affects neurological function and quality of life, and may even cause life-threatening raised intracranial pressure.

Cerebral blood flow (CBF) and the carbon dioxide (CO2) reactivity, are known to be reduced in patients with brain tumor, especially those with pronounced signs of intracranial hypertension.The study reported by Chang et al. showed, that the mean CBF of both hemispheres in each group was not significantly different from brain tumor patients with peritumoral edema to age-matched controls. Cerebrovascular reactivity (CVR) was preserved in patients with mild peritumoral edema but was significantly reduced in patients with moderate and severe peritumoral edema. Surgical removal of the tumor significantly improved the impaired CVR, although the mean CBF did not change.