Betty Brownell

Aberrant nerve fibres within the spinal cord

Raymond (1893), in a necropsy account of a case of syringomyelia, described in the wall of the syrinx small bundles of fine nerve fibres ensheathed with Schwann cells. He traced the origin of these fibres from the posterior root entry zone and decided that they arose from axons of the cell bodies in the posterior root ganglia. Similar findings in syringomyelia were subsequently recorded by Schlesinger (1902), Bischofswerder (1901), Jonesco-Sisesti (1929), and Druckman and Mair (1953). Similar bundles of nerve fibres within and around the spinal cord have been described in other disease processes: in tabes dorsalis by Nageotte (1899), in Potts paraplegia by Fickler (1900), in malignant cord compression by Bielschowsky (1901) and by Druckman and Mair (1953), in traumatic cord lesions by Henneberg (1907), by Roussy and Lhermitte (1918), and by Klaue (1949), in multiple sclerosis by Berchenko (1935), and in cervical spondylosis by Mair and Druckman (1953). These references do not exhaust the world literature, and further instances are given in a review of the subject undertaken by Druckman (1955) for a symposium on regeneration in the central nervous system, held at Bethesda, Maryland, in 1954. Most of these quoted references refer to single instances of this phenomenon which appears to be rare although its exact incidence cannot be stated. In the present paper we record our own observations on the occurrence of these abnormal nerve fibres, illustrated by nine personally studied examples. The principal clinical features and neuropathological findings are given in the Table. In the account that follows we have confined our observations to the detailed microscopical studies of the aberrant nerve fibres.

USE OF MONOCLONAL ANTIBODY PANEL TO IDENTIFY MALIGNANT CELLS IN CEREBROSPINAL FLUID

A panel of monoclonal antibodies was systematically applied to cerebrospinal fluid from 17 patients with suspected neoplastic meningitis and the results were compared with those obtained from routine cytological preparations. The antibody panel consisted of markers for neuroectodermal tissue ( UJ13A ), epithelial cytokeratin ( LE61 ), leucocytes ( 2D1 ), and neoplastic neuroblasts ( UJ181 .4). Additional antibodies were used to refine diagnosis when indicated. Cerebrospinal fluid samples from 12 patients with non-neoplastic conditions were used as controls. The use of monoclonal antibodies gave a positive diagnosis in 16/17 cases and the cells were accurately categorised as carcinoma (5/6 cases), neuroectodermal tumour (8/8 cases), and lymphoma (3/3 cases). In the 14 cases examined by routine cytology, malignant cells were reported in 10 cases and accurately categorised in only 3/14 cases. Immunocytological testing of cerebrospinal fluid with an antibody panel has greatly increased the accuracy with which malignant cells can be identified and categorised.

Immunohistological diagnosis of central nervous system tumours using a monoclonal antibody panel.

A panel of seven monoclonal antibodies has been used to characterise 164 cerebral and spinal tumours. These reagents have enabled rapid and accurate diagnosis of tumours to be made, particularly in cases where standard techniques have proved equivocal. On the basis of characteristic antigenic profiles of tumours, it has been possible to distinguish between gliomas, meningiomas, schwannomas, medulloblastomas, neuroblastomas, choroid plexus tumours, various metastatic deposits, and primary brain lymphomas. The reagents used in the study comprise antibodies binding to (a) most neuroectodermally derived tissues and tumours (UJ13A), (b) fetal brain and tumours of neuroblastic origin (UJ181.4), (c) schwannomas, normal and neoplastic neurones (UJ127.11), (d) glial cells (FD19), (e) epithelial cells (LE61), and (f) leucocytes (2D1). Some reagents, such as antibody A2B5, were less effective as diagnostic markers than originally suggested by previously described specificity. This monoclonal antibody reacted with both neuroectodermal and epithelial derived tumours. The panel of monoclonal antibodies was most useful in the diagnosis of tumours composed of small round cells, particularly lymphoma and neuroblastoma, but the pattern of reactivities allowed most of the central nervous system tumours to be accurately classified. This approach was a valuable adjunct to conventional histological techniques in about 20% of the cases examined.

Neurogenic muscle atrophy in myasthenia gravis

Two cases of severe myasthenia gravis are described, with histological findings. Both cases showed severe neurogenic atrophy of the muscles of the tongue, with fatty pseudohypertrophy and a remarkable proliferation of terminal nerve fibres. Similar, but less severe, changes were present in other bulbar muscles. The findings are in keeping with the view that functional interruption at the neuromuscular junctions results first in failure to transmit the contractile impulse, and at a later stage in denervation atrophy. Terminal proliferation of axons is regarded as an attempt, on the part of motor fibres, to compensate for the breakdown of normal neuromuscular interaction.

Ultrastructure of muscle in Werdnig-Hoffmann disease

Abstract The ultrastructure of denervated muscle from 7 cases of Werdnig-Hoffmann disease (hereditary spinal muscular atrophy of infancy) is described. The diagnosis was established by the clinical finding of amyotrophy and hypotonia in an infant, and electromyographic studies, when performed, showed evidence of denervation in the voluntary muscles. In 3 cases the diagnosis was confirmed at necropsy. Electron microscopy showed changes of denervation in the sarcolemmal nuclei, the sarcolemmal sheath and in the band structure of the muscle fibre. Of particular importance was the demonstration of division of the sarcolemmal nuclei in denervated muscle fibres. The gradual disintegration of the myofibrillar architecture due to a progressive loss of myofilaments was studied. The changes reported are compared with those described in previous reports of the ultra-structure of muscle in cases of Werdnig-Hoffmann disease and Kugelberg-Welander disease, and with those found in denervation atrophy produced experimentally in animals.

The cerebellum in mucopolysaccharidosis: A histological, histochemical, and ultrastructural study

Studies in the morphology, histochemistry, and ultrastructure of the cerebellum, with special reference to the Purkinje cell dendrites, have been undertaken in eight cases of gargoylism. The results suggest that the demonstration of ovoid swellings of the Purkinje cell dendrites by the Cajal method for the cerebellum, together with certain histochemical findings, may enable a diagnosis of mucopolysaccharidosis to be made. Possible mechanisms for the formation of these swellings are briefly discussed.

McArdle's myopathy. A report of a case with observations on the muscle ultrastructure.

Abstract A case of McArdle s syndrome in a 17-year-old male who suffered from muscle cramps and stiffness on moderate exertion is described. The diagnosis of McArdle s syndrome was suggested by the demonstration that the blood lactate failed to rise following exercise and was confirmed by specialised techniques applied to a muscle biopsy. Light microscopy showed peripheral vacuoles in the muscle fibres. Histochemical methods showed an excess of glycogen in the periphery of the muscle fibres and absence of the muscle enzyme phosphorylase. Biochemical analysis of the muscle showed a 3-fold rise in glycogen and the phosphorylase assay gave a result of less than 10% of normal. Electron microscopy showed a gross excess of glycogen situated in the sub-sarcolemmal regions, between the muscle myofibrils and between the individual myofilaments. In the last-named situation the glycogen accumulation was related to the I band and was not seen in the A band. The significance of the clinical, histochemical, biochemical and ultrastructural findings is discussed and methods of diagnosis are suggested. The literature is briefly reviewed.