Dilated Optic Nerve Sheath in Mucopolysaccharidosis I: Common and Not Necessarily High Intracranial Pressure

DISCUSSION

MPSIH is a severe lysosomal storage disease, and one of the earliest manifestations is hydrocephalus. Delayed recognition and treatment can lead to neurocognitive developmental delay or even mortality.^7,8 Moreover, it has been previously shown that the average OP is elevated in the MPSIH cohort compared with the healthy pediatric population.⁹ ONSD has been recognized as a useful, noninvasive measurement to detect elevated intracranial pressure. The subarachnoid space between the optic nerve sheath and the optic nerve widens as the intracranial pressure increases due to its connection to the intracranial CSF. Multiple studies have examined its utility in patients with suspected IIH and have established the average values in pediatric populations and the pediatric IIH populations.^3⇓-5,10

However, there is controversy regarding the best location along the optic nerve for the ONSD assessment, and the technique and measurements often vary from study to study. While most studies report retrobulbar measurements, some authors strongly advocate midpoint measurements. One reason is that histologic studies have shown that the dura close to the globe is more capacious and the dura close to the optic foramen becomes tighter. Eye movement can alter the shape and diameter of the loose dura that is close to the globe. Another reason is that the retrobulbar dura can also be affected by the ocular pathology itself and lead to an increase in the ONSD.¹¹ With greater retrobulbar ONSD in this study, it confirmed the previous finding that retrobulbar ONSDs are larger than midpoint ONSDs due to the larger subarachnoid space in the immediate retrobulbar region than in the midpoint segment posterior to the globe (Table).

Janthanimi and Dumrongpisutikul¹² reported a retrobulbar ONSD of 4.81 mm for 0–1 year, 5.0 mm for 1–2 years, 4.9 mm for 2–3 years, and 5.2 mm for 3–4 years in healthy patients. Shofty et al¹³ measured the midpoint ONSD in healthy children and children with IIH, stratified by age groups. They reported that among children younger than 3 years of age, an average of 3.1 mm was measured in the healthy cohort compared with 4.35 mm in the IIH cohort. Unfortunately, there are no reported reference measurements in the literature in patients with MPSIH. There are prior case series reporting optic nerve edema in more than one-half of the cohort, with 1 study reporting an average retrobulbar ONSD of 5.25–6.71 mm, markedly more elevated than in a healthy population, and another study of 66 patients with the diagnosis of mucopolysaccharidosis I, II, and VI, comparable with the mean ONSD of 5.33 mm in our study.^6,14,15

Contrary to the prevalence of increased ONSD, 1 study reported 30.6% of patients developing hydrocephalus before treatment, with only 16.5% eventually requiring shunt placement.² Therefore, it was unclear whether the mechanism of the increase in ONSD is intracranial hypertension or GAG deposits in the subarachnoid space or a combination of both.⁶

In this study, we examined pediatric patients who did not have shunts and reported average retrobulbar ONSDs of 5.33 mm, which is higher than the previously reported mean in healthy cohorts and patients with IIH.¹³ When the measurements were further broken down by age group, the ONSD in our cohort was larger than that in the study of Janthanimi and Dumrongpisutikul¹² in every patient age group except in the 0- to 1-year group (Table). These findings re-demonstrate the previous finding that the ONSD in patients with MPSIH is larger than that in healthy cohorts. The increase in the ONSD with age also illustrates a similar pattern observed in healthy cohorts, but it is unclear whether the relationship between ONSD and age is a manifestation of normal physiological change or further deposits of GAG (Fig 2).¹³ Most interesting, in our study, a sharp increase in the ONSD was observed from 0–1 year to 1–2 years; perhaps it can be partially explained by a rapid increase in the size of the optic nerve itself in the first 2 years of life.¹⁶

The normal range of OP in the pediatric population has been a subject of debate in the literature. Initially, the proposed normal upper limit of OP in healthy children was <20 cm H₂O, and it was not until 1994 when Ellis¹⁷ performed serial lumbar punctures with the patient in the lateral decubitus position in patients with leukemia and found a mean OP of 19 cm H₂O and a normal range of 10–28 cm H₂O. Recent studies have reported a mean OP of 19.6 cm H₂O, with a range of 11.5–28 cm H₂O, which further suggested that the normal upper limit of OP should be 28 cm H₂O.^18,19 In fact, intracranial pressure of >28 cm H₂O is one of the diagnostic criteria for IIT; the estimated incidence of pediatric IIH is 0.6–0.7 cases per 100,00 children.^20,21 The average OP in our patient cohort was elevated at 22.3 cm H₂O compared with the normal mean of <20 cm H₂O in a healthy population.^17⇓-19 Although there is no established normal OP in the MPSIH population, the OP in this study is comparable with the results in a previous study in which a mean of 24 cm H₂O was reported.⁹ Contrary to the population without MPSIH, there was no statistically significant correlation found between the increased ONSD and increased OP measurements. As illustrated in Fig 1, patients with large ONSDs may, paradoxically, have low OP and vice versa. These findings challenged the notion that the increase in ONSD in patients with MPSIH is purely driven by elevated intracranial pressure (Fig 3). It is possible that GAG deposition and/or inflammatory changes play a role in this finding. Therefore, while elevated ICP is common in MPSIH, increased ONSD does not appear to be an accurate predictor of elevated intracranial pressure.