A case of Werdnig-Hoffmann disease showing extensive sensory involvement after prolonged mechanical ventilation

A 5-year-old boy with Werdnig-Hoffmann disease (WHD), who had been mechanically ventilated for the majority of his life, was examined pathologically. In addition to the classic features of WHD, extensive sensory involvement, including pronounced glial bundle formation in the posterior nerve root, severe demyelination of the posterior column in the whole spinal cord and thalamic neuronal loss were observed. Mechanical ventilation for 5 years prolonged the patient's survival beyond its natural course and produced the unusual pathological findings such as the phrenic motoneuronal loss and severe diaphragmatic and intercostal muscle atrophy. This also appeared to be responsible for the extensive sensory involvement. Data from this case and from previous reports show that WHD is a potential multisystem disorder affecting primarily, but not exclusively, the motor system. We observed marked neuronal accumulation of eosinophilic intracytoplasmic granules in the oculomotor nucleus, substantia nigra, locus ceruleus and nucleus raphe pontis, which appeared as intramitochondrial electron-dense granules on electron-microscopy and myoglobin-positive granules by immunostaining.