‘Pontinization’ of the medulla: two clinical case studies

The anatomy of the pons has been extensively documented [1], and the developmental processes underlying its organization are a topic of intensive study (see [2] for a thorough review). Here, we document two examples of human autopsies where pontine nuclei and associated pontine projection fibres were found not only in the pons, but also in the rostral and mid-level medulla. In effect, the boundary between the ventral pons and ventral medulla is erased, creating ‘pontinization’ of the medulla. In contrast, dorsal pontine and medullary structures appear in normal register and do not overlap. Both cases show normal cranial nerve anatomy, and no other developmental abnormalities are found in the central nervous system. Neither patient was known to have any congenital neurological symptoms, including any signs of abnormal bulbar function. These findings suggest that although embryologic ponto-bulbar development normally proceeds in a stereotyped fashion, a remarkable degree of allowed variability exists which does not appear to have any detectable functional ramifications. This work has previously been presented in abstract form [3]. The first patient (patient A) was a 78-year-old man with a history of dilated cardiomyopathy, congestive heart failure and fibrotic lung disease. He was found unresponsive at his home with no detectable pulse. Emergency medical services restored a pulse, but after arrival at the emergency department, he developed pulseless electrical activity followed by asystole. An autopsy showed a hypertrophic and dilated cardiomyopathy and severe pulmonary fibrosis with superimposed bronchopneumonia, with signs of right-sided heart failure. In addition to the abnormality described in this paper, the brain autopsy showed signs of acute global ischaemia, as well as chronic infarctions in the left superior temporal gyrus and hippocampus, a small number of neurofibrillary tangles in the hippocampus, and a Lewy body in the locus ceruleus. However, it is important to recognize that patient A was not known to have any neurological symptoms other than possible mild dementia; there were certainly no signs of abnormal bulbar function throughout his life. The second patient (patient B) was originally reported as a case record in the New England Journal of Medicine [4]. This patient was an otherwise healthy 45-year-old woman who was recently diagnosed with Hodgkin’s disease, nodular-sclerosis type. Within several weeks she began to develop a burning sensation as well as mild weakness in the distal extremities that soon progressed to total-body pain over the course of several days, with increased limb weakness as well as new bulbar symptoms (difficulty swallowing) and absent deep tendon reflexes. She died of cardiopulmonary arrest with associated aspiration, approximately 9 days after the onset of neurological symptoms. An autopsy revealed disappearance of nearly all the neurones in all the spinal sensory ganglia examined, as well as scattered lymphocytes within the interstitial tissues of the ganglia and their attached nerve fascicles, characteristic of an acute paraneoplastic sensory ganglionitis. Again, all of patient B’s neurological symptoms were acute in onset; she showed no neurological abnormalities prior to the final few weeks of her life. Both patients A and B showed a similar pattern of abnormal pontine anatomy at autopsy. Grossly, patient A’s medulla is notable for being abnormally large, with a prominent, rounded basal surface. On axial cross section (Figure 1A), the medulla has clear inferior olivary nuclei that appear to be encased in firm white tissue. The firm white tissue composes the majority of the rounded, basal surface, and the pyramids are not clearly identified grossly. The pons and midbrain, by contrast, appear relatively normal. Histologically, the basal medulla is infiltrated by white matter tracts and nuclei identical to those normally seen in the pons (Figure 1B,C). These pontine tracts are interspersed around the pyramids, medial lemniscus and inferior olivary nuclei, all of which are normally orientated within the medulla. Note that the cranial nerve nuclei are in their proper locations (Figure 1B – see the hypoglossal nucleus, the dorsal motor nucleus of the vagus and the solitary nucleus and tract). The caudal pons