Interventional News: Advanced Neuroradiology Techniques Improve Children's Outcomes
By Todd A. Abruzzo, MD
Radiology Today
Vol. 19 No. 6 P. 6

Breakthroughs in neuroendovascular treatments are providing hope and healing for children with a wide range of conditions, from hereditary hemorrhagic telangiectasia and Alagille syndrome to pseudotumor cerebri and even retinoblastoma. At the same time, highly precise interventional procedures are enabling providers to treat conditions from the inside out, sometimes eliminating the need for large surgical incisions that may damage healthy tissues. While advances in interventional neuroradiology have improved outcomes for patients of all ages, children and adolescents stand to benefit the most, especially when treated by providers with special expertise in pediatric care. Below are some ways that interventional neuroradiologists at Phoenix Children's Hospital enhance patient care.

Interventional neuroradiologists play an important role in minimizing complications and bleeding during surgery to remove tumors and vascular malformations. In patients with highly vascular tumors or high-flow vascular malformations, it is possible for neurointerventionists to dramatically reduce lesional blood flow before the surgical incision is ever made. This is achieved by positioning microcatheters precisely within the blood vessels that supply the target lesion. The microcatheters are advanced into the appropriate vessels through tiny puncture holes made over the groin or wrist then navigated through the inner channel of blood vessels using image guidance and patient-specific vascular roadmaps. A rapidly solidifying liquid agent or cloud of particles is dispersed into the blood vessel through the microcatheter, a process known as embolization therapy. Different materials are used, depending on the location and type of lesion, but the concept is the same: Materials are "embolized" into the blood supply of the tumor or vascular malformation, selectively blocking blood flow.

This procedure is used for tumors and vascular malformations in the brain, head, neck, and spine. Unlike open surgery, the precision and endovascular nature of the technique allows neurointerventionists to target abnormal blood vessels without disrupting or damaging the surrounding tissue. While open surgery requires doctors to work from the outside in—potentially damaging or disrupting healthy tissues on the way to the surgical site—the neurointerventional approach reaches the surgical site through the inside of an intact blood vessel from a small remote puncture hole. Navigation to the surgical site is accomplished as if traveling underground through a subway tunnel. In some cases, embolization therapy may provide definitive treatment and prevent the need for a major open surgery altogether. This is ideal for lesions that are not resectable, such as deep-seated brain lesions.

Screening for Cerebrovascular Disease
With a focus on screening and recognizing the factors that increase risk, pediatric cerebrovascular specialists can accomplish early detection and treatment of cerebrovascular disease in children. For example, while hemorrhagic stroke due to aneurysms or vascular malformations and ischemic stroke due to embolism are very rare in children, they are more common among patients with specific disease states such as PHACE (posterior fossa, hemangioma, arterial, cardiac, eyes) syndrome, hereditary hemorrhagic telangiectasia, and Alagille syndrome. In all pediatric patients with these conditions, brain imaging studies are used to screen for cerebrovascular disease.

Revascularization Therapies for Stroke
In children who suffer a stroke due to obstruction of a large artery or vein in the brain, irreversible brain damage can be prevented or limited if blood flow is restored quickly enough. Using modern neurointerventional techniques, it is possible to navigate microcatheters into blocked vessels using image guidance and infuse clot-dissolving drugs or mechanically remove the blood clot, ultimately restoring blood flow to the brain.

Infusion Therapies
Cerebral Radiation Necrosis
Patients who have received radiotherapy for central nervous system tumors, metastatic disease, head and neck malignancies, and arteriovenous malformations are at risk of brain radiation necrosis. In effect, the brain tissue surrounding the lesion site is damaged and all of its blood vessels become extremely leaky. The affected brain tissue undergoes massive swelling, the result of an inflammatory cascade that culminates in tissue death. Though rare, necrosis can be a lethal or severely disabling condition, with symptoms including severe headaches, paralysis, seizures, and cognitive impairment.

Treatment options for radiation necrosis are limited. Conventional treatments include high-dose intravenous steroids and intravenous administration of the chemotherapy agent Avastin. Both treatments are associated with severe and potentially debilitating side effects. Hyperbaric oxygen therapy has been used, but its efficacy is not well documented. In some cases, surgery is performed to open the skull and relieve brain swelling, but, once the condition has progressed this far, a poor outcome is likely.

New intra-arterial approaches have shown great promise in the treatment of radiation necrosis of the brain. Using catheter-directed delivery to administer Avastin directly into the circulation of the injured brain, it is possible to stabilize the vasculature, reduce inflammation and swelling, and dramatically reduce the extent of irreversible brain injury, all with minute doses of Avastin. Lowering the dose in this way prevents the severe side effects of intravenous treatment, which requires higher doses.

Pediatric cancer is a major area of focus at Phoenix Children's Hospital, and our division of radiology is now teaming up with oncologists and ophthalmologists to treat children with retinoblastoma. Traditional protocols for retinoblastoma are based on surgical removal of the affected eye (enucleation), radiation, and intravenously administered chemotherapy. If the tumor is extensive and/or vision is irreparably lost, enucleation surgery is usually performed. Removing the affected eye is the provider's best option to ensure the cancer is gone, but the cost of this cure is very high.

Today, a new neurointerventional procedure has been shown to eradicate tumor tissue while preserving the affected eye. Using the same technique of highly precise image-guided catheter placement, we can deliver chemotherapy directly into the circulation of the tumor. Multiple treatment sessions using this new technique have been associated with high rates of ocular salvage and good visual outcomes in patients with intermediate to advanced tumors.

This neurointerventional treatment is much more potent than traditional chemo, as it is localized to the circulation system of the tumor, so it is not diluted into the blood volume of the whole body. Chemo concentration in the tumor tissue is 300 times higher than chemo delivered intravenously, yet the chemo dose to the rest of the body is tiny by comparison. As a result, patient toxicity is minimal, and very few, if any, side effects are experienced.

We believe this technique will create a sea change in the treatment of children with retinoblastoma. Eventually, the hope is to adopt this method to treat tumors in other parts of the body.

Spinal Tumors
For many children, cancer is terminal. They will not get better. It is a heartbreaking situation, and our charge in such cases is to safeguard the child's quality of life while he or she remains alive.

Patients with tumors encircling and invading the spine can be treated with the same interventional neuroradiology technique used for retinoblastoma—targeted microcatheter delivery of chemotherapy directly into the circulation of the tumor. While this won't eradicate the spinal tumors, it will shrink them, preventing severe spinal cord compression. This may save the child from living the rest of his or her life in a state of paralysis.

The hope is that this approach to chemotherapy will eventually become a frontline measure for many other types of pediatric cancers, even curing cancers that today are deemed terminal, while also minimizing the toxicity of therapies such as chemo and radiation.

Vascular Reconstruction
Pseudotumor Cerebri
Some children with chronic headaches suffer from a condition known as pseudotumor cerebri or idiopathic intracranial hypertension. This condition is considered to be the result of excessive accumulation of cerebrospinal fluid around the brain. Generally speaking, the condition results from an imbalance in the production and removal of cerebrospinal fluid. Fluid builds up in the spaces that surround the brain and spinal cord, increasing pressure in the head and causing severe headaches, tinnitus, and progressive vision loss that can eventually lead to blindness.

Patients often are prescribed medication to reduce the production of cerebrospinal fluid and undergo repeated spinal taps to remove cerebrospinal fluid. In many cases, patients undergo a surgical procedure to place a shunt that drains off excess fluid. However, many patients suffer progression of pseudotumor cerebri due to compression of the large veins at the base of the skull. This compression interferes with the normal resorption of cerebrospinal fluid. For these patients, conventional therapies may not solve the problem long term.

New approaches in interventional neuroradiology have proven effective in treating pseudotumor cerebri. For example, in appropriately selected patients with an obstruction affecting the large veins at the base of the skull, neuroendovascular surgeons may insert a stent into affected veins. In effect, this treatment buttresses the veins against collapse or compression.

Young patients with cerebrovascular disease present some of the most complex cases. Managing these conditions requires a highly focused lens to provide care that nurtures growth and development. Working in partnership with providers throughout the hospital system, Phoenix Children's radiologists share a commitment to heal children in the safest and least disruptive ways possible. Neurointerventionists continue to innovate new and better methods to improve diagnosis and treatment, focusing on imaging gently and pioneering new treatments for children whose options are few and far between.

— Todd A. Abruzzo, MD, is an interventional neuroradiologist and the director of neuroendovascular surgery and interventional neuroradiology at Phoenix Children's Hospital.