Consensus-Based Best Practice Guidelines for the Management of Spinal Deformity and Associated Tumors in Pediatric Neurofibromatosis Type 1: Screening and Surveillance, Surgical Intervention, and Medical Therapy.

BACKGROUND: Spinal conditions, such as scoliosis and spinal tumors, are prevalent in neurofibromatosis type 1 (NF1). Despite the recognized importance of their early detection and treatment, there remain knowledge gaps in how to approach these manifestations. The purpose of this study was to utilize the experience of a multidisciplinary committee of experts to establish consensus-based best practice guidelines (BPGs) for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric patients with NF1. METHODS: Using the results of a prior systematic review, 10 key questions that required further assessment were first identified. A committee of 20 experts across medical specialties was then chosen based on their clinical experience with spinal deformity and tumors in NF1. These were 9 orthopaedic surgeons, 4 neuro-oncologists/oncologists, 3 neurosurgeons, 2 neurologists, 1 pulmonologist, and 1 clinical geneticist. An initial online survey on current practices and opinions was conducted, followed by 2 additional surveys via a formal consensus-based modified Delphi method. The final survey involved voting on agreement or disagreement with 35 recommendations. Items reaching consensus (≥70% agreement or disagreement) were included in the final BPGs. RESULTS: Consensus was reached for 30 total recommendations on the management of spinal deformity and tumors in NF1. These were 11 recommendations on screening and surveillance, 16 on surgical intervention, and 3 on medical therapy. Five recommendations did not achieve consensus and were excluded from the BPGs. CONCLUSION: We present a set of consensus-based BPGs comprised of 30 recommendations for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric NF1.

Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females.

Aicardi syndrome is an X-linked-dominant condition characterized by infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae. We reviewed the Aicardi Syndrome Foundation's compilation of family-based, self-reported questionnaires for the year 2000. Information was obtained from 77 females with Aicardi syndrome regarding developmental milestones, seizure frequency, seizure classification, antiepileptic drug use, and medical problems. Patient ages ranged from 1 to 25 years (mean = 7.2 years). All patients were significantly developmentally delayed with milestones ranging from 2 to 36 months. Of the patients, 91% attained milestones no higher than 12 months. Seizures were reported in 92% of patients and occurred daily in 67%. Infantile spasms were the most common seizure type observed in 17%, although a variety of other seizure types were also reported. Multiple antiepileptic drugs were used in these patients with 73% of patients taking two or more antiepileptic drugs. Five patients had a vagal nerve stimulator implanted, and one patient underwent a hemispherectomy. The most common medical problems cited included scoliosis, constipation, gastroesophageal reflux, aspiration pneumonia, and otitis media, but overall health was perceived to be good. Our review demonstrates the spectrum of developmental disabilities, epilepsy severity, and prognosis in a large group of Aicardi patients.

Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is associated with vasculopathy, which may result in a variety of cerebrovascular complications. The purpose of this study was to evaluate the spectrum of cerebrovascular disease in a pediatric population with NF1. Of 316 patients with NF1 who underwent brain MRI, 8 (2.5%) children were reported to have an abnormality of the cerebrovascular system, including narrowed or ectatic vessels, vascular stenoses, aneurysm, and moyamoya.

Neurocognitive dysfunction in children with neurofibromatosis type 1.

The cognitive dysfunction associated with neurofibromatosis type 1 (NF1) is an intriguing aspect of this phenotypically heterogeneous genetic neurocutaneous disorder. A broad range of both nonverbal and verbal learning disabilities are evident in approximately 30% to 65% of children with NF1. Deficits in IQ, executive function, attention, and motor skills have also been documented. Current challenges lie in discovering the underlying multifactorial etiologies of the cognitive abnormalities found in NF1. Likely answers lie in neuroanatomic correlates as seen on neuroimaging as well as in molecular and genetic advances into the role of neurofibromin, the protein product of the NF1 gene. The development of NF1 animal models with learning and memory difficulties similar to those seen in humans demonstrates promising preliminary evidence that medical treatment of cognitive abnormalities may one day be possible.