Decreased cerebrospinal fluid absorption and hydrocephalus in mucopolysaccharidoses: obstructed arachnoid granulations or elevated venous pressure?

Introduction: In mucopolysaccharidosis (MPS) patients, one hypothesis for communicating hydrocephalus is the reduced venous outflow through bone dysostosis of the skull base and chronic dural venous hypertension with impaired CSF absorption. However, it has never been proven. The goal of this study was to determine a correlation between jugular foramina and foramen magnun narrowing, ventriculomegaly and decreased cerebral venous outflow.

Methodology: Forty-three MPS patients (12 MPS I, 15 MPS II, 5 MPS III, 9 MPS IV A and 2 MPS VI) underwent clinical tests and neuroimaging. For the analysis of MRI variables, we measured Evans’ index, third ventricle width, callosal angle, craniocervical junction stenosis, aqueductal and cervical CSF stroke volumes. Ventriculomegaly was defined by an Evans’ index greater than 0.3, a width of the III ventricle greater than 10 mm and a callosal angle less than 90°. The surface area of the foramen magnum and the bilateral jugular foramina was measured using a region of interest surface measurement tool and was dichotomised using median values. Intracranial and extracranial venous mean flow (mL/min) was obtained by using phase-contrast MRI and the adopted cut-off values were: straight sinus < 85, sagittal sinus < 235, right and left jugular veins < 200. This study (13–0252) was approved by the Scientific Committee and the Research Ethics Committee of Hospital de Clínicas de Porto Alegre.

Results: The mean age of the patients was 13.7 years (age range 0.9–36 years). Twenty-five patients were male (58.1%). Severe forms of the disease were found in 13 patients (30.2%). Macrocephaly was present in 32.6% of the patients. The three indices of ventriculomegaly did not correlate with the skull base foramina measurements. Ventriculomegaly, especially the third ventricle width, was associated with reduced venous flow in the sagittal sinus and in the right jugular vein. Also, the decreased venous flow in the right jugular vein was associated with the narrowing of the right jugular foramen and with an increased aqueductal CSF flow.

Conclusions: Based on our results, communicating hydrocephalus in MPS patients seems to be not only related to the obstruction of CSF reabsorption, but it is likely that cortical venous system hypertension due to reduced venous blood outflow through the narrowed right jugular foramen may play a role in the genesis of ventricular dilatation.