Advances in Pediatrics

Neurology & Neurosurgery

Advances in Pediatrics

Strength in Collaboration: NewYork-Presbyterian Pediatric Neurosurgery

Strength in collaboration is the founding principle that launched the recent merge of the two pediatric neurosurgery teams at NewYork-Presbyterian/Columbia University Irving Medical Center and NewYork-Presbyterian/Weill Cornell Medical Center, who have combined their clinical expertise and resources to bring the highest level of excellence to pediatric neurosurgical care and spearhead innovative approaches to common as well as rare, esoteric neurological diseases.

“As a result of this revolutionary partnership, NewYork-Presbyterian is now the largest regional provider of pediatric neurosurgery services in the tristate area,” says Mark Souweidane, MD, Vice Chairman, Department of Neurological Surgery and Director of Pediatric Neurosurgery at New York-Presbyterian/Weill Cornell Medical Center. “Our large volume center brings broader clinical specialization, enhanced patient access, unmatched research and educational opportunities, and surgeons ideally suited for any level of neurosurgical care. Additionally, we are now uniquely poised to develop programs around ill-defined areas of inquiry and rise to an unprecedented level of excellence in the treatment of esoteric disease.”

“No single center can do everything, but a collaboration of both centers spans all disease entities and provides patients with immediate access to our complementary resources, which enables us to treat the most complex and challenging cases,” says Neil A. Feldstein, MD, Director of Pediatric Neurological Surgery at NewYork-Presbyterian/Columbia University Irving Medical Center. “Furthermore, our seamless access to the physicians and services of New York-Presbyterian Morgan Stanley Children’s Hospital and New York-Presbyterian Komansky Children’s Hospital helps us to care for children with multiple challenging conditions, such as a child who has a cardiac problem as well as epilepsy.”

At NewYork-Presbyterian, pediatric neurosurgeons Mark Souweidane, Neil Feldstein, Jeffrey Greenfield, and Caitlin Hoffman partner with experts in multiple other disciplines to form a comprehensive team that addresses patients’ individualized needs. The team’s diverse areas of specialization include hydrocephalus, brain and spinal cord tumors, craniosynostosis, Chiari malformation, tethered spinal cord, epilepsy, and spine deformity (scoliosis). A unifying tenet of surgery for these disorders is the implementation of minimal access surgery as a way of hastening recovery. Devices such as the endoscope, robotics, and surgical planning software serve as the foundation for many of these contemporary approaches, many of which have been advanced by pediatric neurosurgeons at New York Presbyterian Hospital.

“Our shared program accelerates knowledge and clinical expertise across the entire spectrum of pediatric disorders of the brain and spine,” says Dr. Souweidane. “Our multi-institutional approach enables us to add more programmatic structure and develop expertise in very rare conditions including gene therapy, antenatal surgery, movement disorders, cerebrovascular diseases, spasticity, and craniovertebral junction (CVJ) abnormalities.”

Gene Therapy

At NewYork-Presbyterian, Dr. Souweidane and an interdisciplinary team of experts in genetic medicine and child neurology are pioneering safe and effective delivery approaches for viral-mediated gene therapy for children with fatal and developmental neurodegenerative diseases.

“Gene therapy is not new, but its application in the treatment of pediatric neurological disorders is revolutionary,” says Dr. Souweidane, who has achieved international recognition for devising innovative drug delivery techniques for childhood brain tumors and is the principal investigator (PI) for clinical trials using direct delivery as a novel therapeutic approach. “Gene replacement by using safe viral vehicles is impossible using standard routes (oral, intravenous) of administration. Direct delivery to the site of interest is now possible through advances in neurosurgical therapeutic delivery. Because it is critically important to transmit gene therapy to the exact location of the central nervous system, people have come to rely on neurosurgeons who have the expertise to optimize the conveyance of this therapy.”

In 2008, Dr. Souweidane and fellow neurosurgeon Michael G. Kaplitt, MD, PhD, Vice Chair of Research in Neurological Surgery, along with a team of physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center including Ronald Crystal, MD, Chairman of the Department of Genetic Medicine, demonstrated in a clinical trial that viral-mediated gene therapy is safe and effective at slowing the progression of Batten disease, or Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL), a rare, genetic, degenerative neurological disorder that usually becomes fatal in children by the ages of 8 to 12.

“The Batten study demonstrated that our surgical approach, which involves injecting a harmless gene-bearing virus into the brain, was not only safe, but, on the average, significantly slowed the disease progression of the subjects tested,” says Dr. Souweidane. ”Our surgical approach, combined with cutting edge technologies including the ROSA robotic-guided interface and small-scale miniaturized infusion catheters, all contributed to the safe, accurate and expedient distribution of the gene therapy.” 1

Dr. Souweidane is testing this same surgical approach in an open clinical trial that is exploring the use of gene therapy in patients with Mucopolysaccharidosis Type IIIA (MPS IIIA), also known as Sanfilippo syndrome Type A, which is caused by a mutation in the SGSH gene.2 MPS IIIA is a rare, severe condition that causes cognitive dysfunction that gets worse as the child ages, behavioral problems including aggression and hyperactivity, loss of hearing and vision, and sleep disturbances. Children with MPS IIIA rarely survive past their teen years.

“In this Phase 2/3 study, 20 MPS IIIA patients ages 6 months and older will receive a one-time dose of the SGSH gene therapy injected directly to six different sites on both sides of the brain during a single session of neurosurgery,” explains Dr. Souweidane.

Dr. Souweidane and his team will soon be participating in a multi-center study of gene therapy to treat aromatic L-amino acid decarboxylase (AADC) deficiency, a rare, genetic neurometabolic disease that typically appears within the first year of life and is associated with developmental delays, weak muscle tone and seizures. This will mark the first such therapeutic option in North America.

“The field of gene therapy combines hard core science and neurosurgery, which is very exciting,” says Dr. Souweidane. “It is extremely gratifying to know that the research we are doing in gene therapy can improve the quality of life for children who suffer with these esoteric diseases.”

Innovations in Antenatal and Fetal Surgery: In Utero Repair of Myelomeningocele

Driven by an unwavering commitment to find newer and more effective treatments for congenital defects, NewYork-Presbyterian is at the forefront of innovation in antenatal and fetal surgery with minimally invasive approaches to the in utero repair of myelomeningocele, a form of spina bifida associated with a wide range of complications including early death, paralysis, and bowel and bladder dysfunction.

“Our institution supported the Management of Myelomeningocele (MOMS) Study, the NIH-sponsored multicenter clinical study that showed that prenatal surgery significantly reduces the need to shunt fluid away from the brain, resulting in improved mental development and motor function,” says Dr. Feldstein.3 “However, because open surgery is associated with risks to the fetus and mother, we wanted to explore safer endoscopic surgical approaches.”

Known for his pioneering work in Chiari malformation surgery in both pediatric and adult populations, Dr. Feldstein has utilized endoscopic assistance to perform common procedures through smaller incisions in order to decrease operative time and morbidity as well as hospital stay for the management of craniosynostosis, Chiari malformations, and certain forms of hydrocephalus. He is collaborating with Vincent Duron, MD, Pediatric Surgery, Russell Miller, MD and Lynn Simpson, MD, Maternal Fetal Medicine, and Laurence Ring, MD, Anesthesiology, and a multidisciplinary team of experts at NewYork-Presbyterian/Columbia University Irving Medical Center to use fetoscopy for the extremely delicate and complex in utero repair of myelomeningocele.

“We began using one approach, in which the surgeon makes a few small incisions in the mother’s belly and goes through the uterus to perform the surgery on the fetus,” explains Dr. Feldstein. “We then decided to pursue an alternative approach in which we deliver the uterus to perform the surgery fetoscopically. We believe that the second approach is safer for mothers and comparably effective for their infants, and we have been very pleased with the results so far.”

Transitional Care Through the Lifespan of the Child

At NewYork-Presbyterian, the pediatric neurosurgery team takes a multidisciplinary approach that focuses on the whole child and offers them the best opportunity to enjoy a normal transition from child to adult. There is a growing recognition that patients with chronic ailments have an increasing barrier to care by experienced and familiar surgeons as these children age beyond their childhood years.

“Children who have a lifelong need for specialized care, such as those with spina bifida, hydrocephalus, epilepsy and craniofacial disorders, are embraced by our care teams,” says Dr. Souweidane. “Our pediatric neurosurgeons understand the continuous needs of their patients regardless of age and are vested in making certain that the transition from child to adult is simplified by not needing to change care teams. We will work with children through their adolescence, teen years and adulthood to help them understand their responsibility for their health and achieve their personal goals at every stage.”

“Myelomeningocele is a perfect example of a pediatric neurological condition that might require continuity of care,” says Dr. Feldstein. “Children with myelomeningocele often have other neurological problems, and some complications will require regular care or monitoring. Fortunately, these children will not get lost in the shuffle at NewYork-Presbyterian, where we are fully devoted to their continual care to enhance and extend their quality of life.”

Read more Advances in Pediatrics

 

Resources:

1- Souweidane MM1Fraser JFArkin LMSondhi DHackett NRKaminsky SMHeier LKosofsky BEWorgall SCrystal RGKaplitt MG. Gene therapy for late infantile neuronal ceroid lipofuscinosis: neurosurgical considerations.

J Neurosurg Pediatr. 2010 Aug;6(2):115-22. doi: 10.3171/2010.4.PEDS09507.

2- Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA) (AAVance). https://clinicaltrials.gov/ct2/show/record/NCT03612869?cond=Mucopolysaccharidosis+Type+IIIA&draw=2&rank=1

3- Adzick, N.S. et al. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele, N Engl J Med 2011; 364:993-1004
DOI: 10.1056/NEJMoa1014379