Background and purpose Enlargement of the subarachnoid spaces in infancy (ESSI) is a common cause of macrocephaly without proven explanation. We have observed subarachnoid diffusion to be decreased in these patients. We aim to quantify the diffusivity of ventricular and subarachnoid cerebrospinal fluid in ESSI patients, to determine if diffusion characteristics deviate from normocephalic infants, and to propose a unique mechanism for ESSI. Materials and methods 227 consecutive brain magnetic resonance exams from different macrocephalic children were retrospectively reviewed after institutional review board waiver. Patients with noncommunicating hydrocephalus, substantial ventriculomegaly, atrophy, structural bone and/parenchymal abnormalities, abnormal brain signal, hemorrhages, meningitis, and normal imaging were excluded. A total of 53 exams from macrocephalic patients and 21 normocephalic subjects were analyzed. Mean quantitative apparent diffusion coefficient (ADC) values were obtained from the ventricular frontal horn and frontal subarachnoid spaces. The subarachnoid:ventricular ADC ratios were compared using a Mann-Whitney U-test. Results The mean age was 13 +/-8 months (macrocephalic cohort) and 13 +/- 6 months (normocephalic cohort). The subarachnoid fluid mean ADC was 2.50+/-0.26 × 10 mm/s in the macrocephalic group and 2.84+/-0.29 × 10 mm/s in the normocephalic group. The ventricular fluid mean ADC was 2.97+/-0.37 × 10 mm/s and 2.74 +/-0.32 × 10 mm/s, respectively. The mean quantitative ADC ratios in the macrocephalic group were 0.85, significantly smaller than the normocephalic group (1) ( z = -6.3; p = 0). Conclusion Subarachnoid space fluid diffusivity is reduced in patients with enlarged subarachnoid spaces of infancy. We propose insufficient frontotemporal capillary protein resorption to be the initiating factor in ESSI, leading to unbalanced osmotic/hydrostatic pressures, and secondary congestion.

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