Congenital Brainstem Disconnection Associated with a Syrinx of the Brainstem

Abstract

We report a case of congenital brainstem disconnection including the second detailed autopsy. A full-term newborn presented with irreversible apnoea and died on the fifth day. MRI revealed disconnection of the brainstem. The autopsy included a series of transverse sections of the mesencephalon, medulla oblongata and bridging tissue fragments. A fragile tube walled by mature brainstem tissue could be reconstructed. It enveloped a cylinder of fluid within the ventral pons extending to the mesencephalon and the lower brainstem. The aqueduct was patent and outside the lesion. The basilar artery was represented by a tiny median vessel. The ventral and lateral parts of the posterior brainstem were surrounded by heterotopic glial tissue. The olivary nucleus was absent and the cerebellar dentate nucleus was dysplastic. Considering the maturity of the remaining parts of the pons, the onset of structural decline is likely to be close to the time of birth. Probable causes are progressively insufficient perfusion through an hypoplastic basilar artery, and obstructed venous drainage through an abnormal glial barrier surrounding the posterior brainstem. The morphological findings can be characterized as a syrinx, known from disorders in which brainstem or spinal cord are damaged by a combination of mechanical and circulatory factors.

Model Organisms Inform the Search for the Genes and Developmental Pathology Underlying Malformations of the Human Hindbrain

“…For example, brain stem disconnection syndrome (BSDS) has been proposed to also be a segmentation disorder. In this very rare and very severe malformation, the junction of the midbrain and pons or the pons and the medulla are completely discontinuous41,42, a feature not observed in model organisms. In all experimental situations in model vertebrates where hindbrain segments are missing, the remaining transformed hindbrain segments always remain contiguous with each other.…”

Brainstem disconnection associated with nodular heterotopia and proatlantal arteries

“…Case 2 by Sarnat et al 2002 had several malformations including extra‐axial neural ectopia and the convergence of the cerebral crura into a single cord. The case by Barth et al 2008 was associated with cerebellar and olivary hypoplasia, the finding of neural ectopia, and hypoplasia of basilar artery. However, supratentorial anomalies have not been reported.…”

“…Nonspecific cerebellar hypoplasia was noted in all patients. Autopsy has been performed only in two patients [Sarnat et al, 2002; Barth et al, 2008]. Case 2 by Sarnat et al 2002 had several malformations including extra‐axial neural ectopia and the convergence of the cerebral crura into a single cord.…”

“…This condition is usually lethal, its pathogenesis is poorly understood; however some authors have proposed potential genetic or destructive causes [Sarnat et al, 2002]. To our knowledge, only eight patients have been described previously [Mamourian and Miller, 1994; Saint‐Martin et al, 1998; Sarnat et al, 2002; Bednarek et al, 2005; McCann et al, 2005; Poretti et al, 2007; Barth et al, 2008]. We here present an additional patient with disconnection between the pons and medulla associated with cleft palate, periventricular nodular heterotopia, and bilateral persistent proatlantal intersegmental arteries.…”

Deregulated expression of EZH2 in congenital brainstem disconnection

“…Rostro‐caudal limits of the defect vary while the basal pons is always involved and the cerebellum is globally hypoplastic. A recent update and review lists 14 cases, including three brain autopsy studies . Necrosis and glial or inflammatory reactions were absent.…”