An exploratory study of brain function and structure in mucopolysaccharidosis type I: Long term observations following hematopoietic cell transplantation (HCT)

Abstract

Aim Although hematopoietic cell transplantation (HCT) arrests the cognitive decline in mucopolysaccharidosis type IH (Hurler syndrome, MPS IH), these children continue to have neuropsychological deficits as they age. Both compromised attention and effects on white matter have been observed in cancer patients who have had chemotherapy. Therefore, we explored the effects of disease and treatment on brain function in children with MPS I who have had HCT with those with attenuated MPS I treated with enzyme replacement therapy (ERT). Methods Subjects: 7 MPS IH participants at least 5 years post-HCT were compared with 7 attenuated participants who were treated with ERT. Measures: IQ, attention, spatial ability, and memory were assessed. Medical history and an unsedated MRI scan using diffusion tensor imaging (DTI) were acquired. Results Despite clinically equivalent IQ and memory, children with MPS IH had poorer attention span than those with attenuated MPS I as well as decreased fractional anisotropy (FA) of the corpus callosum. A relationship between attention scores and FA was found in the MPS IH group but not the attenuated group. FA was also related to frequency of medical events. Interpretation In children with MPS IH, both the treatment and the disease affect attention functions associated with poor white matter integrity.

Early treatment is associated with improved cognition in Hurler syndrome

“…However, several studies have reported that subsequent cognitive deterioration occurs after stem cell transplantation, justifying the use of intrathecal enzyme replacement therapy to prevent further decline. 32,33 Our results suggest that the decline in IQ observed in some cases may be due to sequelae of early brain injury due to accumulation of glycosaminoglycans. Patients who were younger than 9 months at the time of transplantation had minimal injury and were still cognitively normal; thus, transplantation of stem cells to supply the missing enzyme prevented further injury.…”

Cognitive outcomes and age of detection of severe mucopolysaccharidosis type 1

“…Mild cognitive impairment is common among children with MPS IA, 8,22 particularly in association with the L238Q missense mutation. 8,23 Cognitive outcomes for MPS IA merit further attention by researchers.…”

“…8,17 Even after treatment, children with MPS IH typically perform worse than those with MPS IA on measures of spatial judgment and attention. 22 …”

“…Another study by Shapiro and colleagues 22 reported cognitive outcomes for seven children with MPS IA tested at a mean age of 16 years who had been administered ERT for a maximum of 6 years. The mean cognitive score was 85 (low average).…”

Neurological outcomes after hematopoietic stem cell transplantation for cerebral X-linked adrenoleukodystrophy, late onset metachromatic leukodystrophy and Hurler syndrome

“…Several studies on HSCT in MPS-IH reported improvements in cardiopulmonary function, hearing and vision, and preservation of neurocognitive function 9,14,34 . Some of them documented that subsequent cognitive deterioration might occur after HSCT, mostly if it is performed late 35 .…”