Treatment with Nusinersen and Gene Therapy in a Child with Spinal Muscular Atrophy After Development of Communicating Hydrocephalus


Clinical Other

Poster Number: 5


Joy Lin, MD, Carolina Tesi-Rocha, MD, Richard Gee, Karolina Watson, Mymy Buu


1. Stanford Hospital and Clinics, 2. Stanford University, 3. Stanford Hospital and Clinics, 4. Stanford Hospital and Clinics, 5. Stanford Hospital and Clinics

Background: Since Nusinersen was approved for the treatment of spinal muscular atrophy (SMA) in December 2016, there have been five reported cases of hydrocephalus in patients receiving the therapy [1]. This may not be causative as the SMA disease state may be associated with an increased risk of hydrocephalus [2]. The relationship between development of hydrocephalus and response to treatment is unknown.

Case Description: We describe a two year old child who presented with weakness, constipation, and poor weight gain at 1.5 months. Genetic panel showed no copies of SMN1 and two copies of SMN2, confirming the diagnosis of SMA1. At 2.5 months, she underwent G-tube placement and Nissen fundoplication, was started on BiPAP and cough assist, and began treatment with Nusinersen. After the third treatment at 4 months, she developed rapidly enlarging head size, somnolence, and decreased activity. Her head circumference was 48 cm (100th percentile) on presentation compared to 41 cm (96th percentile) at 2 months. She was found to have communicating hydrocephalus on non-contrast head CT and underwent placement of ventriculoperitoneal shunt with clinical improvement. She had one revision a month later due to leakage. She continued to receive Nusinersen every four months and at two years, she received gene therapy with Zolgensma AVXS-101. Most recently, she finished her 11th treatment of nusinersen and has been doing well, with improvement in motor strength (CHOP-INTEND [2] of 29, compared to 17 prior to initiation of maintenance nusinersen therapy) as well as improvement in pulmonary function (on 13-14 hours of BiPAP a day, compared to 24 hours prior to treatments).

Discussion: We describe a SMA1 patient who underwent shunting after the development of communicating hydrocephalus while being treated with Nursinersen. Despite this complication, she continued to make progress on treatment. Hydrocephalus has occurred in patients treated with Nusinersen intrathecally in the post-marketing setting; however, the contribution of underlying disease to hydrocephalus risk may play a role, as frequency of hydrocephalus in untreated SMA patients appears to be higher when compared to the general population.

[1] Hall S, et al. The incidence of hydrocephalus among patients with and without spinal muscular atrophy (SMA): Results from a US electronic health records (EHR) study. Poster presented at: MDA Clinical & Scientific Conference; April 13-19, 2019; Orlando, FL
[2] New warning of nusinersen-related communicating hydrocephalus. Reactions Weekly 2018;1714:3.
[3] Glanzman AM – Neuromuscul Disord (2010) The Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) test development and reliability.pdf