Infusion-related side-effects during convection enhanced delivery for brainstem-diffuse midline glioma/diffuse intrinsic pontine glioma

Introduction: Side-effects during convection enhanced delivery (CED) are poorly understood. We intended to determine the frequency of side-effects during brain stem infusion and determine risk factors for side-effects persisting longer than 24 h.

Methods: Children with a radiological diagnosis of brain stem diffuse midline glioma/Diffuse Intrinsic Pontine Glioma were treated on compassionate grounds with awake infusion of carboplatin and sodium valproate into the brain stem using the 4-catheter (2 trans-cerebellar 2 trans-frontal) chronic, intermittent Renishaw Drug Delivery System. We used change in the Pontine Neurological Observation Score (PONScore), a standardised neurological assessment tool, to identify side-effects during infusion. Recovery was determined by retrospective chart review.

Results: 55 infusions were performed in 8 children (3-11 years). Mean PONScore increased during infusion from 3.3 to 5.7 (p-value > 0.001). One hundred and fifty-seven infusion-related side-effects were identified including headache (33/157) and limb weakness (49/157). Fifty-four side-effects persisted > 24 h. Side-effects that had occurred during a previous infusion and those that occurred during infusion via trans-cerebellar catheters were more likely to be persistent with OR 2.333 (95% CI 1.094-4.976; p-value = 0.028) and 2.155 (1.029-4.513; p-value = 0.042) respectively. If infusion was stopped or titrated at onset rather than continued, the side-effect was less likely to persist > 24 h, OR 0.473 (95% CI 0.177-0.948; p-value = 0.037). Most side-effects developed within the first three millilitre of infusion.

Conclusions: Side-effects during brainstem infusion are common, can be transient or persist longer than 24 h. Neurological injury during infusion may be time dependent and accumulative rather than volume dependent.