H. H. Goebel

Pigmentoarchitectonic pathology of the isocortex in juvenile neuronal ceroid-lipofuscinosis: axonal enlargements in layer IIIab and cell loss in layer V.

SummaryPigment preparations of 800 μm thickness and Golgi studies of the isocortex in juvenile neuronal ceroid-lipofuscinosis, morphologically proven by electron microscopy, revealed:1.giant axonal dilatations of IIIab-pyramids. These expansions exceeded by far those found in pyramidal cell axons of other isocortical layers;2.severe numerical reduction of neurons in the ganglionic layer.

Confirmation of Virtual Unmyelinated Fiber Absence in Hereditary Sensory Neuropathy Type IV

Sural nerves from two unrelated young boys were virtually without unmyelinated fibers (UFs). Small myelinated fibers (MFs) may also have been slightly reduced in number. Since no degeneration or regeneration is observed, UF absence is assumed to be congenital, due to either lack of neuron formation or to premature degeneration. The main clinical features of this inherited sensory neuropathy (previously identified by us as type IV) are the inherited nature and abnormality of nociception, of sweating, and of thermal regulation associated with mild mental retardation. Our findings confirm the congenital absence of UFs of cutaneous nerves in cases such as these and provide further evidence that this disorder has a different natural history and pathology than do the other three types of hereditary sensory neuropathy.

Eccrine sweat glands are not innervated in hereditary sensory neuropathy type IV

SummaryThe ultrastructural study of a skin biopsy in a patient afflicted with hereditary sensory neuropathy type IV (congenital insensitivity to pain with anhidrosis) did not reveal any unmyelinated axons or axonal terminals around eccrine sweat glands but only proccsses, partially covered by a basement membrane and therefore resembling Schwann cell processes. The absence of such unmyelinated axons in close proximity to eccrine sweat glands where they normally occur appears to be the morphological equivalent to the anhidrosis and also corresponds to the deficiency of unmyelinated axons in the sural nerve of the same patient, as previously reported.

On the ultrastructural diversity and essence of residual bodies in neuronal ceroid-lipofuscinosis

In 4 patients with neuronal ceroid-lipofuscinoses (NCL) (3 patients with the junvenile type, 1 patient with the late infantile type), the ultrastructural spectrum of residual bodies in the central and peripheral nervous system presented curvilinear profiles in all cases and regions investigated and many more ultrastructural patterns within and beyond regions commonly accessible to biopsy, probably due to age dependence, local tissue and cellular biochemical factors. Sampling from basal ganglia especially yielded combined curvilinear-fingerpint bodies, from peripheral ganglia additional membranous bodies. Residual bodies in NCL were present in almost every cell type, similar to the distribution of regular lipofuscin. Although the classical subgroups of NCL contain electronmicroscopically well defined residual bodies, permitting distinction of the late infantile type from the juvenile type, the ultrastructural differences are more of a quantitative than of a qualitative nature. However, they are not pathognomonic. N.m.r. spectra of ceroid and lipofuscin support the concept of their biochemical similarity, and argue against the proposition that they contain a single major component.

Tumor-like amyloid formation (amyloidoma) in the brain

SummaryAn almost walnut-sized tumor was removed surgically from the left occipital lobe of a 46-year-old woman, who had suffered for 4 years from progressive visual loss with scotoma and finally from hemianopia, associated with attacks of headaches and recurrent episodes of depression each lasting for some weeks or months. Neuropathological examination, including polarization, thioflavine fluorescence, immunofluorescence staining, and electron microscopy, revealed an amyloidoma, which consisted of broad appositionally grown amyloid deposits surrounded by some plasma cells, monocytic or foreign body cell types. The massive accumulations, often associated not only with blood vessels or perivascular collagenous fibers but also lying in the cerebral tissue not unlike senile plaques in the cortical gray matter, corresponded to gradually growing masses as seen in the repeated CT scans. This unique lesion in the brain of a patient who did not show any evidence of systemic disorder, seems to confirm that the spontaneous tumor-like amyloid, which gave an immunofluorescent staining mainly with anti-IgM, is a special variant of primary amyloidosis (amyloid L) or of so-called paramyloid (Reimann et al. 1935; Cohen 1967; Azar 1973; Langer and Missmahl 1980).ZusammenfassungEine fast walnußgroße, intra- und subcortical gelegene Masse von Congo-Rot-färbbarem Amyloid mit einigen umgebenden Lympho-Monozyten, Plasmazellen und mehrkernigen Elementen sowie doppelbrechenden plumpen Plaques und fein dispers verteilten Amyloidpräzipitaten innerhalb eines unmittelbar angrenzenden kleinen Rinden-Restgewebes wurde operativ aus dem Occipitallappen entfernt. Aufgrund der typischen grüngelblichen Doppelbrechung im Congo-Rot-Präparat, der Thioflavin-Fluoreszenz, der positiven PAS-Reaktion, Bindegewebsfaserfärbungen und des elektronenmikroskopischen Nachweises charakteristischer unverzweigter 10 nm-Fibrillen kann die Diagnose eines cerebralen Amyloidtumors (Amyloidom) gestellt werden. Bei nur schwacher Anfärbung des vielfach deutlich appositionell gewachsenen Substrates mit Anti-Bence-Jones-Proteinserum (λ-Kette) reagierten die Perikarya der mononukleären lymphoiden Zellen und der Plasmocyten im indirekten Immunfluoreszenztest besonders mit Anti-IgM (FITC-markiert). — Die Trägerin, eine 46jährige Hausfrau, hatte jahrelang recidivierende depressive Episoden und in den letzten 4 Jahren fortschreitende neurologische Symptome nach Art eines chronischen raumfordernden Prozesses ohne jegliche Anzeichen einer Systemerkrankung oder Gammopathie. Sie erholte sich nach der Operation ziemlich gut. Es wird angenommen, daß es sich — analog zum tumorförmigen Amyloid in Haut, Lunge oder anderen Organen — hier um eine isolierte cerebrale Form von Paramyloid oder nodulärer primärer Amyloidose (Amyloid L) im Sinne von Reimann et al. (1935), Cohen (1967), Azar (1973), Langer und Missmahl (1980), Glenner (1980) u. a. handelt.

The Protracted Form of Juvenile Neuronal Ceroid-Lipofuscinosis*

SummaryClinical 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 brothers illness emphasize intrafamilial similarities within subgroups of lysosomal disorders.

Ultrastructural pathology of lymphocytes in neuronal ceroid-lipofuscinoses

Lymphocytes were studied by electron microscopy in five cases of neuronal ceroid-lipofuscinoses (NCL), one of infantile, three of late infantile and one of juvenile types. Each type of NCL revealed specific cytoplasmic inclusions, namely, granular bodies in the infantile form, curvilinear profiles in the late infantile form and fingerprint profiles within vacuoles in the juvenile type. Survey of the literature also confirmed the high correlation between subtype of NCL and type of lymphocytic inclusion. The electron microscopic examination lymphocytes offers easily available diagnostic informations.

Rigid spine syndrome in a girl

SummaryA 15-year-old girl had a lifelong history of moderate proximal muscle weakness, progressively impaired mobility of her spine and limited extension of her elbow joints, compatible with the rigid spine syndrome. Her neck muscles showed a nonspecific myopathy, her biceps muscle type I fiber predominance and type II B fiber deficiency previously demonstrated in the male rigid spine syndrome.ZusammenfassungEin 15jähriges Mädchen litt seit früher Kindheit an einer mäßig ausgeprägten, nur initial progredienten proximalen Muskelschwäche sowie einer fortschreitenden Versteifung der Wirbelsäule und unvollständiger Streckbarkeit der Ellenbogengelenke, vereinbar mit einem „rigid spine“-Syndrom. Histologisch fand sich in der Nackenmuskulatur eine unspezifische Myopathie, während der M. biceps brachii eine Typ-I-Faserprädominanz und einen Typ-II B-Mangel aufwies, wie schon früher beschrieben. Das „rigid spine“-Syndrom ist somit nicht auf männliche Patienten beschränkt.

Becker's x-linked muscular dystrophy. Histological, enzyme-histochemical, and ultrastructural studies of two cases, originally reported by Becker.

SummaryMuscle biopsies of two patients originally reported in the Göttingen family by Becker (1962) that formed the basis of separating a benign X-linked muscular dystrophy from the rapidly progressive Duchenne-type X-linked muscular dystrophy, revealed mild pathological changes in the younger patient and more advanced in the older one, consisting of increased spectra of fiber diameters, endomysial fibrosis, angulated fibers, pyknotic nuclear clumps and small groups of atrophic fibers. Essentially, both biopsies showed the same changes, but of different severity, possibly due to the differences in age and muscle biopsy sites. These changes were regarded “myopathic”, but a neurogenic component was suggested. Our observations accord well with those of a larger series (Bradley et al., 1978) where both electromyography and histopathology revealed a mixed “myopathic-neurogenic pattern” in patients with Becker-type dystrophy. Differential diagnostic aspects encompass Duchennes muscular dystrophy, the other hereditary dystrophies and X-linked proximal spinal muscular atrophies. The precise nature of Becker-type muscular dystrophy requires morphological data on peripheral nerves, spinal roots and spinal cord anterior horn cells as well as sequential biopsy analysis to substantiate the primary site of pathology. However, on the basis of available data, it seems reasonable to suggest that the early changes of degeneration/regeneration which are accompanied by a markedly elevated CPK eventuate in the histopathologic and electromyographic patterns illustrated in these two patients with Beckertype dystrophy.

Congenital muscular dystrophy (CMD) - a collagen formative disease?

Muscle biopsies of 5 patients with congenital muscular dystrophy (CMD) (8 months to 3 years old) were examined by electron microscopy to determine ultrastructural abnormalities of the muscle as well as of the connective tissue cells. Two populations of muscle fibers were observed in each biopsy. Besides muscle fibers with normal or enlarged diameters there were frequently very small muscle cells indicating immaturity. The most interesting findings in each biopsy were myofibroblast-like cells exhibiting active protein synthesis. Large amounts of collagen fibrils with abnormal diameters as well as accumulation of elastic fibrils within the endomysium in CMD suggest abnormalities in collagen synthesis.