A familial neuronal disease presenting as intestinal pseudoobstruction.

The purpose of this paper is to describe 2 siblings who had a generalized neurological disease which presented as intestinal pseudoobstruction. The siblings had 40-year histories of abdominal pain, distention, and vomiting as well as gait ataxia, small, irregular, poorly reactive pupils, dysarthria, absent deep tendon reflexes, and impaired vibratory and position senses. Compared with age-matched controls, they had inappropriate blood pressure responses to phenylephrine, the Valsalva maneuver, and upright posture, lack of sweating on warming, and pupillary denervation hypersensitivity. Radiographs revealed hyperactive, nonpropulsive contractions of a dilated esophagus and small intestine and extensive colonic diverticulosis. Esophageal manometry recorded repetitive, spontaneous, nonperistaltic waves and positive Mechyolyl tests. Postmortem examinations showed degeneration of the myenteric plexuses of the esophagus, small intestine, and colon of both patients. Myenteric plexus neurons were significantly reduced in number compared with 7 controls. About one-third of the siblings' neurons contained round, eosinophilic intranuclear inclusions, which, by histochemistry, were composed of protein by lacked RNA, DNA, carbohydrate, and fat. By electron microscopy the inclusions consisted of an irregular array of nonviral, nonmembrane-bounded filaments. Neurons and glial cells of the brain, spinal cord, dorsal root, and celiac plexus ganglia contained identical intranuclear inclusions. Intestinal smooth muscle was normal. These 2 siblings represent a unique disease in which degeneration of the myenteric plexus resulted in hyperactive but uncoordinated smooth muscle activity and the clinical syndrome of intestinal pseudoobstruction, the presenting manifestation of their neurological disease.