Role of Indocyanine Green with FLOW 800 in Removal of Hidden Arteriovenous Malformations.

OBJECTIVE: Indocyanine green videoangiography (ICG-VA) with FLOW 800 (Carl Zeiss AG) has been used as a visualization tool to guide arteriovenous malformation (AVM) surgery since 2011. We performed a systematic review and evaluated the quality of evidence available on this topic. In addition, we present a series of our own cases demonstrating the unique use of ICG-VA in the localization and removal of deeper seated AVMs. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines for systematic reviews, we identified studies related to ICG-VA with FLOW 800 in AVM surgeries using search terms. The studies were screened and reviewed, and the quality of evidence was analyzed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. We performed a retrospective review of our own cases of AVM removal with ICG-VA and FLOW 800. RESULTS: Our search revealed 27 relevant studies, 17 of which met our inclusion criteria. The quality of the body of evidence was determined to be "very low" using the GRADE criteria. We used ICG-VA with FLOW 800 analysis for 14 cases of microsurgical AVM removal. This technique provided unique insights into the localization of deep seated AVMs in 8 cases (57%). No residual AVM was found when assessed by the 6-month follow-up angiogram. CONCLUSIONS: We present cases highlighting the usefulness of this technique for the localization of certain AVMs. We believe the use of ICG-VA can guide the removal of deeper seated AVMs, because it can reveal surface feeders and draining veins that can be followed to a hidden nidus. Larger, registry-based studies are needed to confirm these findings and improve the overall quality of evidence.

Impaired prenatal motor axon development necessitates early therapeutic intervention in severe SMA.

Gene replacement and pre-mRNA splicing modifier therapies represent breakthrough gene targeting treatments for the neuromuscular disease spinal muscular atrophy (SMA), but mechanisms underlying variable efficacy of treatment are incompletely understood. Our examination of severe infantile onset human SMA tissues obtained at expedited autopsy revealed persistence of developmentally immature motor neuron axons, many of which are actively degenerating. We identified similar features in a mouse model of severe SMA, in which impaired radial growth and Schwann cell ensheathment of motor axons began during embryogenesis and resulted in reduced acquisition of myelinated axons that impeded motor axon function neonatally. Axons that failed to ensheath degenerated rapidly postnatally, specifically releasing neurofilament light chain protein into the blood. Genetic restoration of survival motor neuron protein (SMN) expression in mouse motor neurons, but not in Schwann cells or muscle, improved SMA motor axon development and maintenance. Treatment with small-molecule SMN2 splice modifiers beginning immediately after birth in mice increased radial growth of the already myelinated axons, but in utero treatment was required to restore axonal growth and associated maturation, prevent subsequent neonatal axon degeneration, and enhance motor axon function. Together, these data reveal a cellular basis for the fulminant neonatal worsening of patients with infantile onset SMA and identify a temporal window for more effective treatment. These findings suggest that minimizing treatment delay is critical to achieve optimal therapeutic efficacy.