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Delivery of Antibodies into the Murine Brain via Convection-enhanced Delivery
Published on: July 18, 2019
Infusion-related side-effects during convection enhanced delivery for brainstem-diffuse midline glioma/diffuse
Milo Hollingworth1,2, Stergios Zacharoulis3
1Department of Neurosurgery, Queens Medical Centre, Nottingham University Hospital NHS Trust, Nottingham, NG7 2UH, UK. milo.hollingworth@nottingham.ac.uk.
Insights
Side-effects are common during convection-enhanced delivery (CED) brainstem infusions in children with diffuse midline glioma. Promptly stopping or adjusting infusions reduces the risk of persistent side-effects, suggesting time-dependent neurological injury.
Area of Science:
- Pediatric neuro-oncology
- Neurosurgery
- Drug delivery systems
Background:
- Side-effects of convection-enhanced delivery (CED) for brainstem tumors are not well understood.
- Determining the frequency and risk factors for persistent side-effects is crucial for patient safety.
Purpose of the Study:
- To assess the frequency of side-effects during brainstem infusions in children with diffuse midline glioma/diffuse intrinsic pontine glioma.
- To identify risk factors associated with side-effects persisting longer than 24 hours.
Main Methods:
- Utilized the Pontine Neurological Observation Score (PONScore) to monitor side-effects during awake infusions of carboplatin and sodium valproate.
- Employed a 4-catheter system (Renishaw Drug Delivery System) for chronic, intermittent brainstem infusions.
- Retrospectively reviewed patient charts to determine side-effect recovery.
Main Results:
- 55 infusions in 8 children revealed a significant increase in PONScore during infusion (p < 0.001).
- Common side-effects included headache and limb weakness; 54/157 side-effects persisted beyond 24 hours.
- Previous infusion side-effects, trans-cerebellar catheter use, and continued infusion were associated with longer-lasting side-effects (p < 0.05).
Conclusions:
- Brainstem infusions via CED commonly cause side-effects, which can be transient or prolonged.
- Neurological injury appears to be time-dependent and cumulative, rather than solely volume-dependent.
- Intervention at the onset of side-effects, such as stopping or titrating the infusion, reduces the likelihood of persistence.
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.
