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A 48-year-old man with rapid onset of fever elevation developed acute myelitis over a period of a week. MRI of the spinal cord revealed a longitudinal T 2 -hyperintense intraspinal lesion extending from C6 to Th8 level. Clinical symptoms and findings resolved with immunotherapy. In serological analysis, no antibodies related to various collagen diseases, anti-aquaporin-4 (AQP4) antibody and anti-myelin oligodendrocyte glycoprotein (MOG) antibody were detected. Anti-lactosylceramide (LacCer) antibodies were detected in the acute phase of serum and cerebrospinal fluid, with titers showing decrements in the recovery phase. The present case supports the notion that acute myelitis can occur as an anti-neutral glycolipid antibody-related disorder. Anti-neutral glycolipid antibodies should be examined in future pertinent cases of myelitis.

We report a case of acute disseminated encephalomyelitis (ADEM) concomitant with polyneuropathy associated with anti-lactosylceramide antibody. A 68-year-old man was admitted to our hospital with ophthalmoparesis, bulbar palsy, tetraplegia after suffering from upper respiratory infection and headache. Subsequently, he developed respiratory failure requiring mechanical ventilation. Fluid-attenuated inversion recovery (FLAIR) MRI showed high intensities in the pons and medulla, and a nerve conduction study revealed motor-dominant axonal polyneuropathy. Although the laboratory tests revealed the presence of anti-lactosylceramide antibody in his serum, he was diagnosed with acute disseminated encephalomyelitis concomitant with polyneuropathy. Whereas the intensive treatment with corticosteroids, plasmapharesis, and high-dose intravenous immunoglobulin (IVIg) brought a moderate improvement, his tetraparesis continued to exist.

A 59-year-old man had been admitted to another hospital because of diplopia and thirst at the beginning of March and was diagnosed with diabetic ketoacidosis. He was referred to our hospital because he had limb weakness, dysarthria, and bilateral sensory impairment of the upper limbs, which worsened rapidly from the middle of March, although plasma glucose had been well controlled after the initiation of insulin therapy in the previous hospital. Contrast spinal MRI in our hospital revealed hyperintense lesions at the level of C4 to C5 and T10. The level of myelin basic protein was high (1,260 pg/ml) in the cerebrospinal fluid and serum anti-neurofascin antibody was negative. Nerve conduction study showed typical findings of demyelination at least 2 regions. Although anti-neurofascin antibody was negative, he was diagnosed with combined central and peripheral demyelination (CCPD) based on these clinical findings. After the repeated methylprednisolone pulse therapy for five times, the hyperintense lesions of the spinal cord disappeared gradually. He was bedridden at the beginning of his hospitalization but could ambulate with a cane on discharge 2 months after the admission. Then we received the result of anti-galactocerebroside antibody test as positive. This case suggested that high-dose steroid pulse therapy is safe and may be effective for anti-galactocerebroside antibody-positive CCPD.

Many researchers now recognize the importance of glycobiological research achievements. Glycoside-containing substances such as proteins (glycoproteins) and lipids (glycosphingolipids) have been involved in many important and essential events for normal life. The production of glycoside residues of the proteins is only partially regulated by the genes. In this talk, I will make a brief description of what glycobiology can influence the future of neurological research arena and how glycoproteins and glycolipids affect the normal biology of the neurons. Furthermore, I will introduce you some evidences that many neurological disorders such as Alzheimer's disease and immune-mediated encephalitis have special relationships with glycobiological abnormalities. I also explain the structures and functions of lipid rafts, caveolae, and glycosynapse and their roles in the intracellular signal transduction and cell motility.

Hypertrophic pachymeningitis (HP) is thought to have an autoimmune etiology but its precise cause and treatment remains to be elucidated. Here, we report the clinical details and therapeutic responses of 3 patients with HP and reviewed 66 previously reported cases in the literature. Among these patients, headache was the most frequent complaint. Cranial nerve involvement was also frequently observed, with the optic nerve being the most frequently impaired followed by the oculomotor, trochlear, and abducens nerves in frequency. Elevated C-reactive protein levels and erythrocyte sedimentation rates were found in approximately 97% of the patients. Steroids were the most commonly prescribed therapy, but no definite protocols for the standard dose and duration in HP have been proposed thus far. The average initial dose of prednisolone (PSL) was 42.7 mg/day, and the average maintenance dose was 12.4 mg/day in the chronic stage. Recurrence occurred in many patients when the dose of PSL was reduced to under 20 mg/day. Therefore, steroids should be tapered extremely slowly.

A 58-year-old man was admitted to our hospital with fever, vomiting and disturbance of consciousness after common cold-like symptoms for 2 days. Physical examination showed high fever, moderate hypertension and tachycardia. There were no superficial lymph nodes swelling nor skin rashes. Cerebrospinal fluid (CSF) examination revealed increased protein level (467 mg/dl) and pleocytosis (508 cells/mm3), but no glucose was detected. CSF smear test detected the pneumococcus. Intravenous cefotaxime was administered along with intravenous immunoglobulins and steroid pulse therapy. However, DIC developed, so FOY therapy was started. With these treatments, level of consciousness gradually improved and he became able to eat. At 11th days after the onset, the patient suddenly developed left facial palsy and paresis of the left arm. Head T2-weighted magnetic resonance imaging demonstrated tumor-like hyperintensity signal lesions (28 x 16.6 mm) with ring enhancements in the right frontal lobe. Acute disseminated encephalomyelitis (ADEM) was diagnosed based on MRI and CSF findings, and then additional corticosteroid pulse therapy was administered twice. Herpes simplex virus and herpes zoster virus DNA in the CSF were undetectable by PCR. After 6 days of treatment with corticosteroid pulse therapy, left facial palsy and paresis of the left arm gradually improved and MRI showed the disappearance of tumor-like hyperintense signals. Although ADEM usually develops as a complication after viral infection such as measles, rubella, mumps and herpes zoster, this case suggests that ADEM complication should be considered even after pneumococcal meningoencephalitis.

An 18-year-old female had common cold and insomnia in early March 1987. Later, abnormal speech and behavior, emotional incontinence, anorexia and consciousness disturbance appeared. On March 19, she was admitted to our hospital in semi-comatose state. Myoclonus-like movement on hands was observed, and epileptic attacks with tonic and clonic convulsions occasionally occurred. There were no neurological findings that suspected cerebral focal lesions. The respiration was assisted through tracheal intubation. Laboratory examinations showed inflammatory reactions (CRP+2, WBC 10,600) and transient high levels serum CK (6,215 IU). As she had bradycardia (30-40/min) with complete AV block on ECG, the pacemaker was implanted. The complication of myocarditis was suspected. EEG showed bilateral slow waves (3-6Hz), dominantly in frontal areas. Brain CT and CSF examinations were normal. After the combined administration of ara-A, dexamethasone and anti-convulsant, the consciousness level was recovered within a month. The serum antibody against coxsackie virus B4 alone was significantly increased. We concluded that coxsackie virus B4 caused acute encephalitis with mental symptoms and myocarditis with AV block. Recently, cytomegalovirus was reported to be the causative virus in a young female with non-HSV encephalitis who showed mental symptoms with good prognosis, but coxsackie virus B4 should also be considered as one of the causative viruses.

To address the pathogenesis of GM1 gangliosidosis, especially adult form, intracellular signal transduction pathway of EGF in skin fibroblasts from patients with this disorder was examined. For this purpose, skin fibroblasts from 2 different patients with adult form of the disorder and from 4 different normal controls were used. The results showed that 1) EGF-receptor autophosphorylation was diminished in skin fibroblasts from patients with altered time course of phosphorylation-dephosphorylation reaction. 2) The amount of EGF-receptor protein was decreased in cells from patients compared with that of controls. 3) 125I-EGF binding + internalization studies revealed decreased rate of EGF binding and internalization in patient cells. 4) Ribosomal S6 protein phosphorylation was strongly enhanced in naive cells from patients, but the reactivity to EGF was diminished compared with control cells. These data strongly suggest that patient fibroblasts have abnormalities in the intracellular signal transduction pathway of EGF. This paper is considered to be the first report demonstrating abnormalities in EGF-signal transducing system in human disorders.

A case of 55-year-old man pathologically proven as neoplastic angioendotheliosis was reported. He initially developed sensory disturbance and motor weakness in the lower extremities. After admission, he showed progressive deterioration of higher brain functions with moderate fever. Routine laboratory examinations revealed elevated serum LDH level and erythrocyte sedimentation rate without leukocytosis or increased serum globulin level. Immunological tests were normal, except positive RA. Immunocytochemical investigation of tumor cells in the blood vessel gave the results that these cells appeared to be derived from B cells. Southern blot analyses of the brain samples revealed clear positive bands corresponding to JC virus DNA in the blot. JC virus has been known to infect the endothelial cells of the blood vessel as well as urethral epithelial cells. We discussed the possible mechanism of the selective growth of tumor cells in the blood vessel in terms of possible JC virus infection to the endothelial cells of the blood vessel and abnormal recognition between tumor cells and endothelial cells.