Degenerative changes in unmyelinated nerve fibers in late-infantile neuronal ceroidlipofuscinosis. A morphometric study of conjunctival biopsy specimens.
Late-infantile neuronal ceroidlipofuscinosis (LINCL) is an autosomal recessive disease involving rapidly progressive myoclonic epilepsy, mental and motor regression and progressive visual failure. Neurodegeneration and deposition of fluorescent lipid bodies are the neuropathological hallmarks of this disease. In this study we examined the conjunctival biopsy (CB) specimens of three siblings and two unrelated patients with LINCL. At the time of examination each of three siblings presented a different stage of the disease. The unrelated patients were examined at an advanced stage of LINCL. The findings in these patients are compared to the normal data derived from analysis of seven age-matched 9- to 41-month-old healthy subjects. In young children with LINCL the distribution of unmyelinated fiber (UF) diameter is unimodal. In advanced disease there is a bimodal distribution and a significant reduction of UF density and of relative UF area. As the disease progresses, degenerative changes can be demonstrated: at first a diffuse UF swelling, followed by a decrease of UF density and finally the increase of regenerates (microaxons). These changes, however, seem to reflect an unspecific reaction to nerve injury. They can be demonstrated in a variety of conditions of different pathophysiology such as diabetes mellitus, crush injury and normal aging. This is the first morphometric study of CB specimens. Normal data of UF distribution (unimodal, mode at 0.4-0.6 micron) and UF density (1447,760 +/- 19,347/mm2) in CB specimens correspond well to age-specific data published on the sural nerve.
Schuelke
M
M
Virchow Klinikum, Children's Hospital, Department of Neuropediatrics, Berlin, Germany. mschue@ukrv.de
Cervós-Navarro
J
J
D002675:Child, Preschool; D003228:Conjunctiva / Q000098:blood supply / Q000294:innervation / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009412:Nerve Fibers / Q000473:pathology* / Q000648:ultrastructure; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000473:pathology*; D009679:Nuclear Family; D012016:Reference Values