Cerebellar heterotopia of infancy in sudden infant death syndrome: an observational neuropathological study of four cases

Jakob Matschke,Klaus Püschel,Nadine Wilke,Markus Glatzel,Jan-Peter Sperhake

doi:10.1007/s00414-020-02316-x

Abstract

Sudden infant death syndrome (SIDS) is the sudden unexpected death of an infant < 1 year of age that remains unexplained after comprehensive workup including complete autopsy and investigation of the circumstances of death. The triple risk hypothesis posits that SIDS results as a combination of both intrinsic and extrinsic factors on the background of a predisposing vulnerability. Neuropathological examination in the past has focussed mainly on the brainstem as the major player in respiratory control, where subtle findings have been linked to the chain of events leading to death in SIDS. The cerebellum has received less attention, probably due to an assumed negligible role in central cardiorespiratory control. We report four cases of SIDS in which neuropathological investigation revealed cerebellar heterotopia of infancy, a distinct malformation of the cerebellum, and discuss the potential impact of this condition on the aetiology and pathogenesis of SIDS.

Highlights

Sudden infant death syndrome (SIDS) is defined as any sudden unexpected death of an infant < 1 year of age “with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including performance of a complete autopsy and review of the circumstances of death and the clinical history” [1,2,3]
Since all four cases remained unexplained after complete autopsy and review of the circumstances of death, conceptually, all may be ascertained as SIDS according to the San Diego classification, or as unexplained sudden death in infancy (USDI) following the most recent suggestions from 2019 [3]
cerebellar heterotopia in infancy (CHOI) is defined as the misplaced and/or disorganised aggregation of mature or immature neuroepithelial cells in the cerebellum [25, 26] In our cases, the lesion was located near the midline in 3 cases, and in one case laterally in the cerebellar hemisphere, in accordance to findings described in the literature [26]

Summary

Introduction

Sudden infant death syndrome (SIDS) is defined as any sudden unexpected death of an infant < 1 year of age “with onset of the fatal episode apparently occurring during sleep, that remains unexplained after a thorough investigation, including performance of a complete autopsy and review of the circumstances of death and the clinical history” [1,2,3]. Considering recent advances in our understanding of the physiology of cerebellum, its role in the chain of events leading to death in SIDS may have been underestimated and warrants further investigation History This 3-month-old male infant was found lifeless lying in supine position in a bed, which he had shared with his mother. Microscopy was unremarkable except for a focal group of misplaced mature neurons with Purkinje cell-like features in the white matter of cerebellar vermis (Fig. 1b) History This 7-week-old male infant had been completely healthy until his father took him for a walk in a baby sling and finding him lifeless on returning. History This 8-week-old female infant had been in complete health prior to death when the father wearing the girl in a baby sling noticed her lifeless on returning from a walk. An aggregation of disorganised and misplaced cerebellar tissue was seen (Fig. 1d), accompanied by findings compatible with olivary heterotopia in the medulla oblongata (not shown)

Discussion

Compliance with ethical standards