NEW SUBFORM OF THE LATE INFANTILE FORM OF NEURONAL CEROID-LIPOFUSCINOSIS

Clinicopathological studies of a series of nine children with a new su bform of Jansky-Bielschowsky disease or late infantile neuronal ceroid lipofuscinosis (LINCL) is presented. The onset of this subform is bet ween 2.5-3.5 years of age with initial neurological symptoms of abnorm al motor skills caused by cerebellar and extrapyramidal signs. Soon af ter dementia, myoclonic seizures are followed. Visual impairment is mo re clearly seen after the age of 5 or 6 years. The ultrastructural stu dies of the skin and/or buffy coat showed abundant lysosomal storage o f curvilinear profiles, rarely intermixed with fingerprint profiles. T he MRI of the head performed in seven cases, showed initially enlargem ent of the ventricles that is secondary to basal ganglia atrophy and p resence of cerebellar and cerebral atrophy. In 4 of 7 cases (Cases 1, 5, 6, 8) abnormalities in the deep white matter showing increased sign als of T2-weighted imaging in the periventricular areas of the fronto- parietal region, internal capsule, tracks of the brainstem, and white matter of cerebellum were seen. These abnormalities were also observed by post-mortem neuropathological studies in three cases (nos. 7-9). T he MRI in Cases 7 and 9 was not performed. The electrophysiological ab normalities (EEG, ERG, VER) are similar as described in the classical LINCL. Neuropathological studies done in 3 of 9 cases showed generaliz ed brain atrophy and unique type of neuronal cytoplasmic inclusion bod y in the basal ganglia, brainstem, dentate nuclei, and rarely, cerebra l cortex. These large, round neuronal cytoplasmic inclusions were pink in hematoxylin (HE), violet in cresyl violet, and dark blue with Kluv er-Barrera method. They were unstained with ConA and distinctly varied ranging from negative to strong positive with Sudan BB. These lysosom al inclusions correspond to unusually densely packed curvilinear profi les which in some cells formed large aggregates almost entirely fillin g the neuronal cytoplasm. Neurons of other grey matter regions, howeve r, showed loosely arranged curvilinear profiles that were surrounded b y single membranes and sometimes intermixed with fingerprint profiles, similar as described in the classical LINCL cases. The cerebellum sho wed unusually severe atrophy. This new variant of jansky-Bielschowsky disease stresses the heterogeneity within this particular subform of L INCL. Further biochemical and genetic studies are needed to better def ine these different subforms of NCL cases.