Abstract
Enzyme replacement therapy (ERT) has limited therapeutic effects on neurologic, skeletal,
and cardiovascular pathophysiology. We report an acute right-sided flaccid hemiparesis
in an 11-year-old boy with the severe neuronopathic phenotype of Hunter's syndrome
who was receiving weekly idursulfase ERT. Due to his psychomotor regression and epilepsy,
his presentation to the hospital was delayed. Computed tomography scan of brain showed
no acute changes or hemorrhage. Stroke code was not called as patient was already
outside of the time window for tissue plasminogen activator (tPA) therapy. Brain magnetic
resonance imaging (MRI) showed diffuse cortical and deep atrophy consistent with his
baseline neurological status and restricted diffusion in the territory of the left-middle
cerebral artery (MCA) consistent with recent infarction. T1-weighted MRI revealed
low signal intensity of the left insular cortex, as well as volume loss, consistent
with previous undiagnosed stroke in the same vascular territory. In addition, MR angiogram
(MRA) demonstrated left terminal M1 segment MCA occlusion. Echocardiogram showed aortic
root dilation and moderate aortic valve insufficiency. Patient was also noted to have
bacteremia related to port infection. ERT is limited by blood–brain barrier and the
underlying glycosaminoglycans (GAGs) extracellular tissue accumulation which produces
a proinflammatory state. GAG and bacterial lipopolysaccharide (LPS) are known to activate
toll-like receptor 4 (TLR-4). GAGs released in the extracellular space of intracranial
vessels induce inflammation by activating the TLR-4 pathway which is exacerbated by
bacterial LPS contributing to focal arteritis. Our case suggests the importance of
GAGs in the activation of the TLR-4 pathway as a cause of stroke in Hunter's syndrome.
Keywords
cerebrovascular accident - mucopolysaccharidosis type II - enzyme replacement therapy
- idursulfase - toll-like receptor 4 - glycosaminoglycans
