Spontaneous Third Ventriculostomy in Krabbe Disease

Abstract

Introduction: Spontaneous third ventriculostomies have been reported in relation to obstructive hydrocephalus and increased intracranial pressure and are most commonly seen as disruption of the floor of the third ventricle. Hydrocephalus has been reported in patients with Krabbe disease; however, it is clinically difficult to monitor for hydrocephalus in patients with Krabbe disease as symptoms of increased intracranial pressure may overlap with symptoms of Krabbe disease. We describe a case series of spontaneous third ventriculostomy and hydrocephalus, likely in response to increased intracranial pressure, in patients with infantile Krabbe disease.

Methods: Brain magnetic resonance images of patients with infantile Krabbe disease were retrospectively analyzed to assess for ventricular size and presence of spontaneous third ventriculostomies. A brain atlas was used to standardize the calculation of ventricular size. Mid-sagittal, T2-weighted images around the third ventricle were assessed for spontaneous third ventriculostomies. Developmental outcomes were measured with a series of standardized and validated tests.

Results: Seventy-five patients with infantile Krabbe disease were evaluated. Twelve cases of spontaneous third ventriculostomies were identified. Head circumference (SE = 8.07; P < 0.001) and average ventricular volume were greater (left: SE = 1.47, P < 0.001) in patients with spontaneous third ventriculostomies when compared with patients without spontaneous third ventriculostomies. Patients with spontaneous third ventriculostomies also had more delayed development in adaptive (difference = 0.2, P < 0.01), gross motor (difference = 0.0, P < 0.01), and fine motor (difference = 0.1, P < 0.001) function.

Conclusions: Spontaneous third ventriculostomies, likely in the context of increased intracranial pressure, were identified in patients with Krabbe disease. Although difficult to assess, our study highlights the importance of monitoring for increased intracranial pressure, which can result in spontaneous third ventriculostomies, in patients with infantile Krabbe disease.

Keywords: Globoid cell leukodystrophy; Intracranial pressure; Krabbe disease; Spontaneous third ventriculostomy.

Figure 1.

Representative sagittal images demonstrating a large flow void and focal defect in the floor of the third ventricle consistent with STV in four patients with Krabbe disease. The arrowhead indicates the location of STV.

Figure 2.

Head circumference over time among male and female patients with Krabbe disease, stratified by the presence and absence of STV. Each point depicts an individual measurement; lines connecting points show multiple measurements for an individual child. The black line represents the mean curve for typical developing children. The red line indicates patients with STV and the blue line patients without STV.

Figure 3:

(A) Right ventricular volume over time stratified based on the presence and absence of spontaneous third ventriculostomy (STV). Each point depicts an individual measurement; lines connecting points show multiple measurements for an individual child. The red line indicates patients with STV and the blue line patients without STV. (B) Left ventricular volume over time stratified based on the presence and absence of spontaneous third ventriculostomy (STV). Each point depicts an individual measurement; lines connecting points show multiple measurements for an individual child. The red line indicates patients with STV and the blue line patients without STV.