Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures

To study the demyelinative effects of antibodies to glycolipids, well-myelinated cultures of mouse spinal cord tissue were exposed to antisera against galactocerebroside and two gangliosides (GM₁ and GM₄), as well as to anti-white matter antiserum. The demyelinative process was evaluated by morphologic and biochemical techniques. Cultures exposed to anti-white matter and anti-galactocerebroside antisera showed the most marked changes. These consisted of a decrease in the number of oligodendroglial cells and dissolution and phagocytosis of myelin. Concomitantly, the activity of 2′,3′-cyclic nucleotide-3′-phosphohydrolase (CNPase) was decreased by 60–70%. This occured within 24 h of exposure to a relatively low concentration of serum (10%). Cultures exposed to anit-GM₁ and anti-GM₄ antisera showed similar changes but to a lasser degree. The CNPase activity was decreased about 30% within 48 h of exposure to a 25% concentration of these antisera. This diminution represents about a 20% loss of myelin, an observation corroborated by electron microscopy where myelin but not oligodendroglial cell was observed. Therefore, in addition to anti-galactocerebroside activity, which was previously found to be the major antibody responsible for the demyelinating activity induced by anti-whole CNS tissue antiserum, these data suggest that antibodies to gangliosides like GM₁ and GM₄ might also play a role in immune-mediated demyelination, including perhaps, the human demyelinating diseases.     

Computed tomography in late-onset metachromatic leucodystrophy

Summary In late-onset metachromatic leucodystrophy (MLD), early clinical diagnosis is difficult since initial symptoms frequently consist of misleading nonspecific psychopathological alterations. On cranial computed tomography (CT), however, symmetrical attenuation decrease of the white matter and mild cerebral atrophy can already be found in an early stage of the disease, and may even precede clinical symptoms. On the basis of observations in four patients with late-onset MLD who were followed between 1 and 5 years, characteristic CT appearances in different stages of the disease are outlined and compared with the literature.     

Experimental allergic encephalomyelitis in guinea pig: variability of response to intradermal emulsion injection

Different forms of experimental allergic encephalomyelitis were obtained in 4 groups of guinea pigs: 7 adult Hartley guinea pigs (Group I), 12 adults of the same strain (Group II), 6 juvenile strain 2 guinea pigs (Group III) and 6 juvenile strain 13 animals (Group IV), by the injection of emulsions. Groups I and II received emulsions containing 250 mg and 500 mg respectively of fresh isologous spinal cord tissue, complete Freund adjuvant (CFA) and saline solution while Groups III and IV received an emulsion containing 120 mg of isologous spinal cord, CFA, saline solution and 15 mg of Mycobacterium tuberculosis. The increased antigen load induced a disease with delayed onset and prolonged progressive course (C-P-EAE) in Groups I and II, although 8 animals showed no symptoms of illness. The findings in C-P-EAE were large demyelinated plaques, perivenous fibrosis and large areas of infiltration. Demyelinated areas occurred within the spinal cord white matter only in two asymptomatic animals. C-P-EAE was obtained in 4 of the Strain 2 animals. In conclusion, the increased antigen load induced a range of lesions in Hartley guinea pigs, although not all animals were affected. C-P-EAE was induced also in strains of guinea pig other than the Heartley strain. These different reactions may have been the outcome of partial or complete inactivation of the cell-mediated response to the inoculated antigens.

---

Sommario Differenti forme di encefalomielite allergica sperimentale sono state realizzate in quattro gruppi di cavie con iniezione di emulsioni: il primo gruppo era di 7 cavie di tipo Hartley, il secondo era formato da 12 adulti dello stesso ceppo, il terzo da 6 soggetti di ceppo giovanile 2 e il quarto da 6 animali del ceppo giovanile 13. I gruppi 1 e 2 ricevettero emulsioni contenenti rispettivamente 250 e 500 mg. di tessuto midollare isolago fresco con composto di Freund e soluzione salina mentre i grouppi 3 e 4 ricevettero un'emulsione con 120 mg. di midollo e gli altri componenti e in più 15 mg. di mycobacterium tubercolosis. Nel gruppo 1 e 2 si sviluppò una forma morbosa con ritardato avvio e un decorso prolungato e progressivo, benché 8 animali non abbiano presentato sintomi di malattia: si riscontrava nelle cavie malate la presenza di placche vaste di demielinizzazione con fibrosi perivenosa ed area estesa di infiltrazione. In 2 animali asintomatici si è constatata un'area di demielinizzazione nella sostanza bianca del midollo. La stessa forma a lento avvio e a decorso prolungato e progressivo si è verificata in 4 animali del ceppo 2. Risultò cosi che l'aumento degli antigeni ha prodotto importanti lesioni negli animali tipo Hartley anche se non tutti gli animali presentarono sintomi di malattia e lo stesso tipo di malattia è stato indotto anche in ceppi di cavie di tipo non Hartley. Queste reattività differenziate possono essere il risultato di una parziale o completa inattivazione della risposta mediata delle cellule agli antigeni inoculati.

     

肿瘤样脱髓鞘病3例临床病理分析

目的探讨肿瘤样脱髓鞘病临床和病理学特点。方法对3例肿瘤样脱髓鞘病患者的临床特征进行了分析,并对活检脑组织进行了组织病理学和免疫组化研究。结果3例患者均呈亚急性起病,临床表现各不相同,有复发缓解过程。头部MRI显示3例患者分别在额、顶叶及小脑半球单发大面积病变。组织病理学观察均显示中心区组织高度水肿,呈空泡样变,有囊性坏死区。白质髓鞘高度崩解,轴索相对保留完好。免疫组化染色显示大量炎性细胞主要是淋巴细胞及少量单核吞噬细胞围绕血管呈袖套样浸润。结论肿瘤样脱髓鞘病临床表现各异,当影像学表现为孤立、单发、巨大病灶时,应想到脱髓鞘疾病的可能,病理学检查对确定诊断有重要价值。     

Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily.

Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparison with MOG N-terminal peptide sequence. As expected, MOG mRNA expression is CNS-specific and peaks during active myelination. Our studies show that full length MOG mRNA is approximately 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N-glycosylation is found at Asn-31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N-terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B-G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig-like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members.     

Overriding fifth finger: an unusual sign in lower brachial plexopathy

Hand deformities are often useful clinical signs. To our knowledge, they have not been described in association with brachial plexus lesions. A 28-year-old female presented with sudden left shoulder pain and medial forearm parasthesia. Examination showed the left fifth finger adducting and flexing over the dorsal aspect of the fourth finger. Neurophysiological studies and MRI supported a brachial plexus lesion. The physical sign was not present 5 months post onset and the patient experienced near complete clinical improvement. The unusual physical sign occurred in association with neuralgic amyotrophy. Its occurrence can be explained in terms of transient patchy involvement of nerve fascicles in the brachial plexus.     

Vascular thermocoagulation — perivascular nerve lesions an ultrastructural report on the choice between monopolar and bipolar electrocoagulation

Summary High-frequency coagulation is used with advantage for a number of purposes, including the production of haemostasis during surgery. The morphological changes which thermocoagulation produces in or near the wall of an artery remain, however, largely unknown; and systematic research in the subject is long overdue.As might be expected from clinical experience, the local effects of monopolar thermocoagulation are much more severe and far-reaching than those caused by the bipolar method. For these reasons the bipolar coagulation technique is to be preferred wherever possible.     

The effects of the growth factor‐antagonist, trapidil, on remyelination in the CNS

In this study we describe the effects of trapidil, a putative platelet‐derived growth factor‐antagonist, on spontaneously occurring remyelination in rat spinal cord. Demyelination was created in the dorsal funiculus of 6‐ and 11‐week‐old female rats by the direct injection of 1.0 μl of 1% lysolecithin. The animals received daily intra‐peritoneal injections of either trapidil or saline for 21 days, commencing on the day of lesion induction. The 11‐week‐old rats receiving trapidil (60 mg/kg) showed a significant decrease in the extent of oligodendrocyte remyelination. Moreover, those axons that were remyelinated by oligodendrocytes tended to have thinner myelin sheaths than axons remyelinated by oligodendrocytes in the control group. In the 6‐week‐old group, the dose of trapidil which inhibited oligodendrocyte remyelination in the 11‐week‐old animals had a minimal effect on the extent of oligodendrocyte remyelination and no effect on the quality of myelin sheath formation. A higher dose of trapidil (80 mg/kg) was required before significant impairment of oligodendrocyte remyelination was achieved in the younger age group, implying an age‐dependent effect of growth factor‐inhibition of CNS remyelination. These results indicate an important role for growth factors, and in particular PDGF, in the orchestration of oligodendrocyte remyelination in the rodent CNS.     

Clinicopathological differences between juvenile and late infantile metachromatic leukodystrophy

The autopsy report of the juvenile type of metachromatic leukodystrophy is rare. The clinical and pathological difference between the juvenile and the late infantile type of metachromatic leukodystrophy was described. Loss of myelin sheaths was much less in the brain stem and spinal cord in the juvenile type than in the late infantile type, although that of the roots or cranial and spinal nerves was marked similarly in both types. The relationship of these pathological findings to clinical signs and laboratory data was discussed.     

A simple method for high resolution light microscopy of nervous tissue

A simple method for high resolution light microscopy of nervous tissue is described. Tissue perfused with glutaraldehyde and formaldehyde and postfixed with osmium tetroxide is embedded in HistoResin (LKB Bromma), a new glycol methacrylate based embedding medium, and sectioned (2 microns) on a standard microtome. The method gives excellent preservation of tissue structure, which is far superior to that in paraffin sections and in fact resembles that in epoxy resin-embedded material. It does not, however, require the time, expertise and ultramicrotome needed to cut epoxy resin sections. This technique is particularly useful for assessing demyelination.