In December 2016, Nusinersen (Spinraza▼) was first authorised as an antisense oligonucleotide indicated for the treatment of 5q spinal muscular atrophy. During therapy intrathecal nusinersen is given by lumbar puncture as 4 loading doses on days 0, 14, 28, and 63 followed by maintenance doses every 4 months.
During routine clinical use of nusinersen, 5 cases of communicating hydrocephalus have been reported up to 6 July 2018 worldwide. Of the 5 cases, 4 were children with spinal muscular atrophy type 1 with signs of hydrocephalus which developed after 2 to 4 loading doses and one was an adult with scoliosis. Cerebrospinal fluid (CSF) drainage procedures was required in 3 of the children and continued nusinersen treatment (2 had ventriculoperitoneal shunts) and one child did not require a CSF shunt and is being monitored post discontinuation of nusinersen.
Between spinal muscular atrophy and communicating hydrocephalus there is no known association and investigations did not reveal an underlying cause such as intracranial haemorrhage or infection.
Approximately 1,437 patients have received nusinersen in routine clinical practice (439 patient-years) up to 30 September 2017 worldwide. No reports of hydrocephalus associated with nusinersen treatment received in the UK although usage is currently very limited.
The risk of communicating hydrocephalus and its clinical features should be discussed with patients and their caregivers. They are advised to seek urgent medical attention if any signs or symptoms of hydrocephalus develop including persistent vomiting or headache, seizures, decreased consciousness, or a rapid increase in head size in children.
Hydrocephalus should be considered in the differential diagnosis of any patient with suggestive clinical features and confirmed cases should be referred urgently to a neurosurgeon for advice on further management.
The effectiveness and safety of nusinersen in patients with CSF shunts has not been determined. If nusinersen is continued, prescribers should continue to monitor the response to therapy. If a CSF shunt is required, patients and their carers should be informed that the risks and benefits of continued nusinersen treatment in patients with CSF shunts are not known.
Healthcare professionals are asked to report any suspected adverse drug reactions to nusinersen on a Yellow Card, including signs or symptoms of hydrocephalus or any problems developing after insertion of a CSF shunt.
