Infantile type of so-called neuronal ceroid-lipofuscinosis

Summary Autopsy reports are presented of three cases of a rapidly progressive encephalopathy with clinical onset around one year of age, early amaurosis, and microcephaly. Convulsions were few or absent. The disorder led to an extraordinary degree of brain atrophy, due to total loss of neurons from the cerebral and cerebellar cortex, and an advanced degree of neuronal destruction in most subcortical centres. The giant cells of Betz and the primary motor and sensory neurons were notable exceptions. The surviving neurons, other neuroectodermal cells, and a number of extraneural cell types showed accumulation of autofluorescent sudanophilic granules, resistant to lipid solvents, in their cytoplasm. Ultrastructurally, these granules were of the residual body type, consisting of membrane-bound conglomerations of spherical globules 0.2–0.5 m in diameter, with a homogeneous, finely granular internal structure. These lesions were associated with a pronounced astrocytic and mesenchymal reaction with the presence of large numbers of phagocytic cells in the grey matter of the CNS and, to a lesser extent, in other tissues. In addition, there was almost total loss of myelin from the brain, apparently due to Wallerian degeneration.The characteristic clinical, histological and ultrastructural features differentiate this condition from other progressive encephalopathies of the age group in question, including the late infantile type of the Batten-Vogt syndrome. Recent ultrastructural and biochemical findings indicate that the disease of our patients is identical with the progressive encephalopathy with disturbed polyunsaturated fat metabolism described by Hagberget al. (1968).     

Infantile type of so-called neuronal ceroid-lipofuscinosis. 2. Morphological and biochemical studies

Morphological and biochemical data are given on brain biopsy or autopsy samples from 13 patients with a progressive encephalopathy, characterized clinically by the onset of rapid psychomotor deterioration at about 1 year of age, early amaurosis, and absence or relative paucity of convulsions.The main morphological feature was very severe neuronal destruction, accompanied by a massive occurrence of frequently binucleated phagocytes and unusually hypertrophic fibrillary astrocytes in the cerebral cortex. The remaining neurons and glial cells contained excessive amounts of autofluorescent granules with the staining properties of lipofuscin, and with strong acid phosphatase activity. The homogeneous granular ultrastructure of the storage material differed both from ordinary neuronal lipofuscin and from the storage material in most previous reports on so-called neuronal ceroid-lipofuscinosis. Biochemically the biopsy samples were characterized by a decrease in lipid-bound N-acetylneuraminic acid.Thus, the unusual but uniform clinical, morphological and biochemical findings in our series of 13 patients differ from the findings in previously recognized types of amaurotic idiocy. These 13 patients—and possibly some others collected from the literature—appear to constitute a clearly separable group; the relationship of this condition to various forms of neuronal ceroid-lipofuscinosis is discussed.     

Adult type of neuronal ceroid-lipofuscinosis with retinal involvement

A rare case of Kufs' disease with retinal lesions is reported in which the first symptom of visual disturbances later resulted in total blindness. Various neurologic symptoms and mental deterioration also developed. The total duration of the illness was 32 years. Neuropathologic examination showed extensive ballooned nerve cells filled with lipopigments in the CNS. In the retina there was a thinning with severe loss of rods, cones, and outer nuclear and outer plexiform layers. The remaining ganglion cells of the retina were also ballooned and accumulated with lipopigments. Histochemical and electron microscopic examinations disclosed that the lipopigments in the ballooned neurons of the CNS and the retina were identical with lipofuscin pigments.     

Late-infantile neuronal ceroid-lipofuscinosis. An ultrastructural study of lymphocyte inclusions.

Ultrastructural study of peripheral blood from two patients with late-infantile neuronal ceroid-lipofuscinosis with curvilinear bodies, demonstrated in brain biopsies revealed curvilinear bodies in lymphocytes. These findings indicate that ultrastructural investigation of circulating lymphocytes may be useful in the diagnosis of late-infantile neuronal ceroid-lipofuscinosis and may circumvent the need for brain biopsy. Curvilinear bodies were also present in the lymphocytes of a neurologically normal younger female sibling of patient 1, who has had a single seizure, leading to speculation that she may be in the early stages of the same disease. This case suggests the possibility of early detection of this disorder and indicates the importance of screening lymphocytes of siblings of affected patients. Tubular cytoplasm inclusions were present in a high percentage of lymphocytes of the asymptomatic parents and a younger sibling of these patients.     

A dominant form of neuronal ceroid-lipofuscinosis

Summary The study of the ultrastructure of the sural nerve and peripheral blood lymphocytes of a boy with late-infantile neuronal ceroid-lipofuscinosis revealed the presence of curvilinear bodies and fingerprint profiles. The elder sister of the patient died at the age of 7 years after progressive mental and motor deterioration. The same kind of cytoplasmic inclusions was found in the lymphocytes of the father of these children, who had had epilepsy since the age of 32. Clinical data and the results of the ultrastructural study suggest that in the same family two different forms of ceroid-lipofuscinosis appear and that the disease is inherited as an autosomal dominant trait. This family seems to suggest the nosological unity of clinically different forms of ceroid-lipofuscinosis.This work was supported by AMDA grant 1979–1980     

Deposits of neuronal ceroid-lipofuscinosis in transitional structures--electron microscopic study

Deposits of neuronal ceroid-lipofuscinosis in two cases were studied using the electron microscopy. The structure most frequently observed in both cases was a curvilinear body containing fingerprint patterns. Other structures, such as the granular pattern, zebra body-like structure and vacuole, were also observed less frequently. A loose pattern, which had an intermediate curvature between the fingerprint pattern and curvilinear body, was found for the first time. They might play an important role on the morphogenesis in the deposit of neuronal ceroid-lipofuscinosis.     

The so-called ectopic pinealomas. A cooperative study of 15 cases.

We present the results of a cooperative study of 15 cases of suprasellar dysgerminomas (ectopic pinealomas) and a review of cases of the literature with histological confirmation. In all the cases, histological similarities to the germinomas which appear extracerebrally, particularly testicular seminomas, were observed. We were unable to find in the sellar region tumors of true pineal histology and tend therefore to confirm the germinal origin of these neoplasms. From a clinical point of view, we define a syndrome that these tumors produce, consisting of diabetes insipidus as the first sign, visual impairment and endocrine disturbances, with few or no radiological signs in plain studies.     

The first case of infantile type neuronal ceroid-lipofuscinosis in Japan]

We reported the first case of typical infantile-type neuronal ceroid-lipofuscinosis (INCL) in Japan. The patient was a 1-year-old girl presenting with rapidly progressive psychomotor deterioration and blindness. Muscular hypotonia, microcephaly and myoclonic jerks became marked with the progression of her disease. Diminution in amplitude of EEG, VEP and ERG was prominent in the initial stage, but ABR was normal. MRI showed progressive brain atrophy. Electron microscopic examination of the biopsied skin revealed granular matrix, the specific inclusion bodies, in the epithelial cell of sweet glands. Many sea-blue histiocytes were demonstrated in her bone marrow samples. INCL is a common progressive encephalopathy in the Scandinavian countries, but a typical case had not yet been fully reported in Japan. This prompted us to report our case. Future reports are need for the study of INCL in Japan.     

Light and electron microscopic study of juvenile neuronal ceroid-lipofuscinosis lymphocytes

We report the findings of a light and electron microscopic follow-up study of lymphocytes from 10 patients with juvenile neuronal ceroid-lipofuscinosis. Vacuolated lymphocytes observed by electron microscopy varied from 34-67% in 22 different specimens from 10 patients. Although the percentage of vacuolated lymphocytes increased with duration of the illness in 5 of 6 patients who were younger than 11 years of age, there was no such tendency in 4 patients who were older than 13 years. This result may indicate that vacuolated lymphocytes increase with the duration of illness until an age of saturation. Three to 46% of lymphocytes contained lipopigments consisting of granular matrix and fingerprint profiles which were unrelated to age. Lymphocytes with fingerprint profiles constituted less than 12% of the total and could not be found during examination of 100 lymphocytes in 6 of 22 specimens.     

Lymphocyte ultrastructure in two cases of neuronal ceroid-lipofuscinosis.

Circulating blood lymphocytes from two patients with neuronal ceroid-lipofuscinosis (NCL) were investigated by transmission electronmicroscopy. Ultrastructural examination showed two forms of intracytoplasmic single membrane-limited inclusions. Contents of the first inclusion form were arranged in five distinct patterns: (1) granules, (2) membranous formations, (3) paracrystalline forms, (4) alternating electron-dense/electron-lucent arrangements, and (5) admixtures of these components. These molecular morphologies suggest the usefulness of lymphocyte fine structure as a diagnostic tool in NCL. The second inclusion form contained cylinder-like structures. These structures are not specific for NCL and have been identified in other diseases.     

Infantile spasms in patients with neurofibromatosis type 1

The authors report two patients with neurofibromatosis type 1 who were affected by infantile spasms. The infantile spasms were severe and unresponsive to anticonvulsant treatment. The authors maintain that infantile spasms may belong to the clinical features of neurofibromatosis type 1.     

The protracted form of juvenile neuronal ceroid-lipofuscinosis

Summary Clinical and ultrastructural findings consisting of curvilinear and fingerprint residual bodies, in a protracted juvenile form of NCL are reported from a woman who died at the age of 35 years. Homochrony and homotypy of her brother's illness emphasize intrafamilial similarities within subgroups of lysosomal disorders.This study was supported in part by the Deutsche Forschungsgemeinschaft, SFB 33.     

An adult case of canine neuronal ceroid-lipofuscinosis

Summary Intraneuronal accumulation of cytosomes with the fluorescent and tinctorial properties of ceroid-lipofuscin occurred in the C.N.S. of a fully matured dog with signs of slowly progressive cerebellar disease. Ultrastructural study revealed various membrane-bound inclusions in addition to typical lipofuscin granules. The clinicopathologic findings in this case were contrasted with those occurring in English Setters with juvenile neuronal ceroid-lipofuscinosis, and compared with those reported in Kufs' disease in man.     

Studies in neuronal ceroid-lipofuscinosis: Heterogeneous nature of neuronal autofluorescent lipopigments

A method has been developed for the complete extraction and fractionation of the autofluorescent lipopigments present in the neuronal tissue of Batten-Spielmeyer-Vogt (BSV) patient and normal subject, respectively. The fluorescent lipopigments that were about three-fold higher in BSV patient's brain as compared with normal subjects were separated into at least 7 fluorometrically and chromatographically distinct fractions by thin layer chromatography (TLC). Although the fluorescent lipopigments of the brain tissue of BSV patient and normal subject showed identical pattern of separation on TLC, the fluorescence spectra of the individual lipopigment fractions from BSV patient was different from those of the corresponding fractions from the normal subject. The ultraviolet spectral studies with individual fluorescent lipopigment fractions indicated the presence of highly unsaturated conjugated chromophore.