engleski

Werdnig-Hoffmann disease: The loss of anterior horn neurons of the spinal cord unbiasedly estimated using the disector method

Werdnig-Hoffmann disease (WHD) is an infantile type of spinal muscular atrophy characterized by progressive denervation of skeletal muscles. In an attempt to quantify the loss of anterior horn neurons of the spinal cord in children who died of WHD, we performed this pilot-study using a statistically robust probe, called the disector (Sterio DC, J. Microsc. 134:127, 1984). The spinal cords of a five month old female, who died due to the early-type of WHD, and of a three month old female, who died of non-neurological cause were, after fixation, embedded in paraffin wax, sectioned at 20 microns and stained with cresyl- violet. Following random systematic sampling the sections were optically disected by two rectangular planes (reference and "look-up" plane) separated by known vertical distance, which was measured with a digital length gauge. The neurons counted came from the clearest nuclear profile which fell within this volume and did not touch either of two forbidden lines or "look-up" plane. By multiplying the numerical density and the reference volume (measured using the Cavalieri principle), the total number of neurons was obtained. The number of neurons in the child with WHD was significantly lower than in the normal control (including calculated shrinkage difference). The difference represented a loss of about 34% of the neurons. This finding, for the first time, quantifies neuronal loss in cases of WHD, although more cases should be analyzed before drawing valid conclusions. We conclude that the number of neurons could serve as a valuable parameter for evaluating the severity of the disease. In addition, reliable data on neuronal number in other neural structures could shed more light on the pathogenesis of this disorder.

spinal muscular atrophy ; neuron loss ; disector method ; stereology ; alpha-motoneurons ; spinal cord

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