Brainstem Disconnection: Two Additional Patients and Expansion of the Phenotype

Abstract

Brainstem disconnection (BD) is a rare posterior fossa abnormality defined by the nearly complete absence of a brainstem segment with the rostral and caudal brainstem portions connected only by a thin cord of tissue. The outcome is poor and the majority of children die within the first 2 months of life without achieving developmental milestones. We report on the cases of two children with BD and a prolonged spontaneous survival. Neither patient required intubation or mechanical ventilation and each survived longer than 2 months (one child died at the age of 8 months, the other is alive at the age of 4.5 years). In addition, patient 1 is the only child with BD reported so far who achieved some developmental milestones. Although the long-term neurodevelopmental outcome of BD remains unfavorable, the expansion of the phenotypic spectrum may be important in terms of counseling.

Isolated neonatal bilateral vocal cord paralysis revealing a unilateral medullary defect: a case report

“…Brainstem disconnection is a very rare congenital anomaly of the infratentorial region, defined by an absent brainstem segment. This regional discontinuity may be observed at the pontomesencephalic level but is more common at the pontomedullary level [ 17 ]. Most reports have described extensive defects, with only a thin cord of tissue between the rostral and caudal brainstem portions [ 18 ].…”

“…Other brain abnormalities have been inconsistently mentioned: absence of cerebellar peduncles, hypoplastic or absent optic nerves, absence of internal auditory canals, dilated cisterns or cerebral ventricles, periventricular nodular heterotopia, and hamartoma [ 20 ]. Extracerebral abnormalities, sometimes multiple in a single patient [ 21 ] and notably involving the axial skeleton, heart, and digestive and genitourinary tracts, have been noted in both pontomesencephalic and pontomedullary disconnections [ 17 ].…”

“…The absence of gliotic lesions on histological examination has also been interpreted in favour of this aetiology [ 23 ]. From this perspective, the brainstem dysgenesis results from an abnormal expression of segmentation genes or their upstream modulators at the midbrain-hindbrain boundary [ 17 , 18 ]. Animal models, however, do not unequivocally reproduce segmental dysgenesis [ 24 ], and no mutation of candidate genes, such as EN2, or causative variations on whole exome sequencing have thus far been documented in humans [ 17 , 22 , 23 ].…”

Clinical and neuroimaging features as diagnostic guides in neonatal neurology diseases with cerebellar involvement

“…All children are symptomatic at birth. The clinical manifestations are characterized by brainstem dysfunction including absent or weak sucking and swallowing, absent or markedly insufficient breathing in the majority of patients, increased or decreased muscle tone, and reduced or poor visual fixation [ 27 ]. Seizures and unstable body temperature may occur.…”

“…BD is defined by the characteristic neuroimaging pattern including nearly complete absence of a brainstem segment with the intact rostral and caudal portions connected only by a thin cord of tissue on neuroimaging [ 27 ]. BD is usually associated with cerebellar hypoplasia.…”