Question: Spinal muscular atrophy (SMA) is a clinically heterogeneous neurodegenerative disorder
caused by bilallelic deletions or point mutations in the survival motor neuron 1 gene
SMN1. In 2017, the drug Nusinersen (Spinraza®) was approved for treatment of SMA.
This intrathecally applied drug modifies the splicing of SMN2 and thereby increases
the amount of functional SMN protein. Recognized side effects include post-lumbar
syndrome, pyrexia and thrombocytopenia. Recently, the company announced a hydrocephalus
as a possible side effect in five patients undergoing treatment, but there are no
publications reporting details of these cases. This had promoted concern among physicians
that warrants further evaluation.
Methods: In a retrospective study, we analyzed medical history, clinical information, intracranial
pressure measurements, ophthalmologist and neuroimaging results in 30 patients with
SMA type 1–3 undergoing treatment with Nusinersen at the Department of Pediatric Neurology
of Charité University Medicine Berlin. Ophthalmologist examinations and neuroimaging
were performed routinely following the company’s announcement.
Results: In our cohort none of the patients reported symptoms indicative of increased intracranial
pressure. The lumbar puncture opening pressure (LOP) was above 20 cm H2O in 19 patients
(63.4%), and within this group above 26 cm H2O in 11 patients (36.7%). There were
no signs of increased intracranial pressure in ophthalmological assessments or brain
imaging in patients with increased LOP. Only one patient reported a prolonged phase
of headache after lumbar puncture and showed subtle signs of brain atrophy on cranial
MRI. We did not identify a correlation between increased LOP and scoliosis, sedation
or age of the patients; however, LOP was generally higher in patients with SMA3 (8/11
patients; p = 0.036).
Discussion: The announcement of hydrocephalus as a putative side-effect of Nusinersen treatment
in SMA patients has raised concern in the Pediatric Neurology and Neurology community.
None of the patients in our cohort had symptoms or signs indicative of increased intracranial
pressure. However, about two-thirds of the patients had an increased LOP. Our results
raise the question whether the LOP is generally increased in SMA (also in therapy
naïve patients), what the etiology is, and whether the increased LOP needs to be treated.
Conclusion: Clinicans treating SMA with Nusinersen should be aware of the possible adverse side
effect of hydrocephalus communicans and monitor intracranial pressure and possible
signs of increased ICP.
