Case Study Highlights Complications With Intrathecal Delivery of NPC Drug

Intrathecal drug administration via lumbar puncture and a spinal access port device led to serious complications in a patient receiving experimental therapy for Niemann-Pick type C.

In a case report on intrathecal drug delivery for the neurodegenerative disorder Niemann-Pick type C (NPC), both repeated lumbar puncture (LP) and a spinal intrathecal access port device carried significant risks that must be mitigated as treatments advance.

NPC is a rare autosomal recessive disease caused by variants in the NPC1 or NPC2 gene, leading to accumulation of cholesterol and other molecules in cells over time. The liver, lungs, spleen, blood, gastrointestinal tract, and eventually the brain are affected, and there is no curative therapy for the disease.

The case study reports on a 15-year-old male patient with NPC who had developed symptoms including dysarthria, short-term memory loss, ataxia, and lack of coordination and balance—typical NPC symptoms—and was enrolled in a clinical trial to evaluate the effects of 2-hydroxypropyl-beta-cyclodextrine (2HP-β-CD). The medication, which has shown potential to delay clinical onset and extend patients’ lifespans but has a low capacity to cross the blood-brain barrier, is administered via intrathecal injection every other week.

After 4 months of therapy with occasional headaches, back pain, and leg pain post treatment with LP, a spinal intrathecal access port device was implanted as an alternative to repeated LP. The device was implanted subcutaneously in the right midaxillary line, and the catheter was inserted through the L4-L5 interspinous space. It was secured to the lumbo-dorsal fascia clamps and nonabsorbable sutures.

Catheter migration was the first serious complication. The patient experienced acute pain, swelling, and bruising in the reservoir pocket site 4 days after the device was inserted. He then experienced back pain and a headache, after which imaging studies showed that the catheter had migrated outside of the intrathecal space and had to be surgically removed along with the port.

Treatment via LP resumed, and 10 months later there was further complication. After a regular treatment, the patient suffered from dizziness, confusion, polydipsia, and a prolonged tonic-clonic seizure requiring intubation and sedation. He was diagnosed with severe hyponatremia that was corrected, with no further seizures afterward. However, an MRI of his spine revealed a a subdural hematoma stretching from L1 to S2 that caused lower limb weakness and incontinence due to caudal equina compression.

The patient recovered from the incident but was withdrawn from the trial after the complications due to intrathecal treatment administration. Although mild complications from intrathecal therapy administration are fairly common, both of the serious complications he experienced—especially subdural hematoma—are rare. Even so, less invasive and more efficient drug administration methods are necessary to ensure patients receive the most advanced treatments with fewer complications.

“There has been significant increase in the development of drugs and novel therapies for rare diseases, but unfortunately, the development of better devices (including intrathecal drug delivery devices) has not followed in parallel to that growth,” the authors wrote.


Ciancio J, Aquilina K. Complications associated with intrathecal drug delivery in a paediatric patient with Niemann-Pick type C. BMJ Case Rep. 2021;14(5):e241786. doi:10.1136/bcr-2021- 241786