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Tumefactive demyelination (TD) is a solitary cerebral demyelinating lesion clinically and radiologically mimicking brain tumors. It can occur in isolation or may be rarely associated with other demyelinating diseases. The underlying pathogenic mechanisms are unknown. We present the first report of TD following in-vitro fertilization (IVF) in a 36-year-old healthy woman who developed subacute right hemiparesis shortly after a scheduled IVF cycle. Evaluation revealed left hemispheric space-occupying lesion pathologically diagnosed as TD. Treatment with intravenous methylprednisolone promptly resulted in a clinical and radiological improvement maintained thereafter. This report confirms and expands the spectrum of inflammatory demyelinating conditions associated with IVF and suggests possible hormonal influence in the development of TD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Action myoclonus renal failure (AMRF) syndrome is a rare form of progressive myoclonus epilepsy with renal dysfunction related to mutations in the SCARB2 gene. This gene is involved in lysosomal mannose-6-phosphate-independent trafficking of β-glucocerebrosidase (GC), an enzyme deficient in Gaucher disease. We report a family with myoclonic epilepsy, ataxia and skeletal muscle atrophy but without cognitive impairment or overt renal disease. A novel SCARB2 mutation was indicated by a striking discrepancy between lymphocyte and fibroblast GC activity in the proband evaluated for possible Gaucher disease. Our findings expand the genetic and phenotypic diversity of AMRF and suggest that low GC activity may present an important biochemical clue to the diagnosis of AMRF., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Alpha-fetoprotein (AFP) is an immunomodulatory glycoprotein associated with the normal growth of the mammalian fetus. Ws have shown that treatment with recombinant human AFP (rhAFP) reduced lymphocyte reactivity and the extent of neuroinflammation in mice with experimental autoimmune encephalomyelitis (EAE). In the present study we found involvement of AFP in immune cell apoptosis, attesting to its possible mechanism of action. AFP increased the expression of the Bax, Bid, Bad and ApaF genes in peripheral lymphocytes, together with an enhanced expression of Caspase-3, Fas, FasL and TRAIL among infiltrating immune cells. The induction of apoptosis markers was accompanied with an increased expression of Foxp3 in lymph node cells, as well as accumulation of CD4+Foxp3+ regulatory T cells in the CNS. Overall, these immunological alterations gave rise to a milder disease and accelerated remission rate. Our results suggest a new role for AFP in controlling the autoimmune inflammation associated with EAE.

Background: A 24-week phase II trial has shown that 0.3 mg of laquinimod given daily to patients with relapsing-remitting multiple sclerosis was well tolerated and reduced the formation of active lesions. We assessed the effect of oral daily 0.3 and 0.6 mg laquinimod on MRI-monitored disease activity in a 36-week double-blind, placebo-controlled phase IIb study., Methods: The study was done in 51 centres in nine countries. Inclusion criteria were one or more relapses in the year before entry and at least one gadolinium enhancing (GdE) lesion on screening MRI. Of 720 patients screened, 306 eligible patients were enrolled. Patients, aged 18-50 years, were randomly assigned to placebo (n=102), laquinimod 0.3 mg a day (n=98), or 0.6 mg a day (n=106). Brain MRI scans and clinical assessments were done at week -4, baseline, and monthly from week 12 to week 36. The primary outcome was the cumulative number of GdE lesions at weeks 24, 28, 32, and 36. The principal analysis of the primary endpoint was done on the intention-to-treat cohort. This study is registered with ClinicalTrials.gov, number NCT00349193., Findings: Compared with placebo, treatment with laquinimod 0.6 mg per day showed a 40.4% reduction of the baseline adjusted mean cumulative number of GdE lesions per scan on the last four scans (simple means 4.2 [SD 9.2] vs 2.6 [5.3], p=0.0048); treatment with 0.3 mg per day showed no significant effects (3.9 [5.5] vs placebo, p=0.6740). Both doses of laquinimod were well tolerated, with some transient and dose-dependent increases in liver enzymes. A case of Budd-Chiari syndrome-ie, a thrombotic venous outflow obstruction of the liver-occurred after 1 month of exposure in a patient with underlying hypercoagulability who received 0.6 mg laquinimod. Anticoagulant treatment resulted in a decline of liver enzymes to normal without any clinical signs of hepatic decompensation., Interpretation: In patients with relapsing-remitting multiple sclerosis, 0.6 mg per day laquinimod significantly reduced MRI-measured disease activity and was well tolerated.

Standard CD44 (CD44s) and its alternatively spliced variants (CD44v) were found to be associated with the metastatic potential of tumor cells, and with cell migration of autoimmune inflammatory cells, including cells involved in experimental autoimmune encephalomyelitis (EAE). The aim of the present study was to evaluate whether induction of anti-CD44 immune reactivity, through cDNA vaccination could down-regulate EAE. Our vaccination technique involved the insertion of CD44s or CD44v cDNA into a silicone tube filled with 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of SJL/J mice immunized with myelin antigens for EAE induction. Animals vaccinated with CD44v cDNA developed significantly less severe EAE when compared with sham vaccinated animals or animals vaccinated with CD44s cDNA. The in vitro proliferation of lymphocytes was preserved regarding myelin antigens and mitogens. Histopathological examinations revealed a significant reduction of EAE lesions and enhanced apoptosis in central nervous system (CNS)-infiltrating cells of the successfully vaccinated animals. Such methods of cDNA vaccination with CD44 could be applicable in inflammatory CNS diseases, like multiple sclerosis.

In chronic inflammatory diseases like multiple sclerosis (MS), neuroprotection refers to strategies aimed at prevention of the irreversible damage of various neuronal and glial cell populations, and promoting regeneration. It is increasingly recognized that MS progression, in addition to demyelination, leads to substantial irreversible damage to, and loss of neurons, resulting in brain atrophy and cumulative disability. One of the most promising neuroprotective strategies involves the use of bone marrow derived stem cells. Both hematopoietic and non-hematopoietic (stromal) cells can, under certain circumstances, differentiate into cells of various neuronal and glial lineages. Neuronal stem cells have also been reported to suppress EAE by exerting direct in situ immunomodulating effects, in addition to their ability to provide a potential source for remyelination and neuroregeneration. Preliminary results from our laboratory indicate that intravenous or intracerebral/intraventricular injection of bone marrow derived stromal cells could differentiate in neuronal/glial cells and suppress the clinical signs of chronic EAE. Both bone marrow and neuronal stem cells may therefore have a therapeutic potential in MS. It seems that future treatment strategies for MS should combine immunomodulation with neuroprotective modalities to achieve maximal clinical benefit.

Introduction: Myasthenia gravis (MG) is considered a paraneoplastic phenomenon of thymomas in 15% of patients. Co-existence of MG with extrathymic malignancies, and an increased risk of second malignancy in patients with thymoma have been reported. Data on clinical characteristics of MG patients with extrathymic malignancies and the role of concomitant diseases and their treatment are lacking., Methods: The clinical records of 188 consecutive MG patients were studied retrospectively. We examined whether gender, age, generalized disease, seropositivity for acetyl-choline receptor antibodies, occurrence of thymoma, immunosuppressive therapy and occurrence of other autoimmune diseases determined an increased risk for development of extrathymic malignancy., Results: This group followed the typical epidemiological characteristics of MG. Thirty-three patients (17.6%) had a thymoma. Twenty-nine patients (15.4%) had 30 extrathymic malignant tumors of various origins. Only four patients with extrathymic tumors had an associated thymoma. Tumors were diagnosed between 20 years prior to and 35 years after the appearance of MG. Older age of MG onset was the only risk factor identified for development of malignancy in MG., Discussion: Extrathymic malignancies are common in MG patients, especially in the older age group. There are no specific clinical features of the subgroup of MG patients with cancer. Although MG is not a paraneoplastic phenomenon of extrathymic malignancy, the association between MG and malignancy may be due to a common background of immune dysregulation.

The thalamus is a relay center for afferent sensory pathways that regulates and transmits peripheral stimulation to various representative areas of the cortex. Aphasia, neglect and anosognosia were also reported to occur after thalamic lesions, in the absence of cortical pathology. However, considerable controversy exists as to the pathogenetic mechanisms, and incidence of cognitive abnormalities following thalamic lesions. We present a series of sixteen consecutive stroke patients with thalamic stroke (n=12) or hemorrhage (n=4), admitted to a university based neurology department. Dysphasia was observed in seven of eight patients with left thalamic strokes (five in the territory of the tuberothalamic artery, two inferior-lateral thalamic lesions and one in the area supplied by the anterior choroidal artery). Neglect and anosognosia appeared in five of eight patients with right side thalamic insults (two each in the territories of the tuberothalamic and thalamogeniculate arteries and one in the area supplied by the posterior choroidal artery). These findings reconfirm those found in previous studies and suggest that the thalamus is part of an integral neuronal network concerned with cognitive functions.

The permanent middle cerebral artery occlusion (PMCAO) model was used to investigate the cerebroprotective effects of the synthetic cannabinoid, dexanabinol (HU-211). Dexanabinol is a noncompetitive N-methyl-D-aspartate antagonist, with antioxidant and anti-TNFalpha properties. Twenty hypertensive rats were subjected to PMCAO. Eight were given 4 mg/kg dexanabinol, i.v., 1 h after PMCAO, eight received vehicle and four were not injected Five rats underwent sham surgery. Infarct volumes were assessed, as well as TNFalpha concentrations and NOS activity in brain homogenates. Dexanabinol significantly decreased infarct volumes. It also significantly lowered TNFalpha levels in the ipsilateral hemisphere although not to the level of sham operated rats. No effect could be demonstrated on NOS activity. In conclusion, dexanabinol may be a pluripotent cerebroprotective agent.

We present a case of reflex-induced simple partial seizures, triggered by feelings of frustration, anger and despair. Such emotions were provoked by pondering over complex national and international, political and moral issues. The present case may suggest that activation of right temporal networks may mediate negative and adverse emotions induced by preoccupation with agitating, controversial issues.

In this review we delineate the rationale for immunotherapy in multiple sclerosis and describe the various levels at which immune intervention, according to a modern model of the immune system organization, is feasible. Current and future immunosuppressive and immunomodulating therapeutic approaches at the level of antigen presentation and at the lymphocyte and cytokine network levels are discussed.

Background: Myasthenia gravis (MG) is an autoimmune disorder mediated by antiacetylcholine receptor antibodies. It has long been suspected to exacerbate during the menstrual period but this has never been adequately documented., Subjects and Methods: We questioned 120 female myasthenic patients of different ages, about their myasthenic symptoms before and during the menstrual period. We also evaluated the effect of medications, pain and stress during or before the menstrual period on the exacerbation rate. Exclusion criteria were postmenopausal age and incomplete information available in the questionnaire., Results: Forty two premenopausal women with generalized disease were included in the study. Twenty eight (67%) of the patients reported exacerbation of their myasthenic symptoms 2 to 3 days prior to the menstrual period. This exacerbation persisted in 22 of them to the third day of the menstrual period. In nine of the women this clinical worsening necessitated an increased intake of medications during the days prior to menstruation. No correlation could be found between the presence of antiacetylcholine receptor antibodies, pain, stress, use of oral contraceptives or the type of antimyasthenic therapy and the rate of exacerbation before and during the menstrual period., Conclusions: (1) MG frequently exacerbates before and during the menstrual period in 67% of MG patients. (2) The rate of exacerbation is unrelated to the presence of stress or pain prior to or during the menstrual period. (3) Different therapies directed against MG, as well as oral contraceptives do not influence the clinical course. (4) Menstrual exacerbations occur in both seronegative and seropositive patients. (5) These exacerbations may frequently necessitate therapeutic changes.

Accumulated evidence implies that mutations in the gene coding for Cu/Zn superoxide dismutase (SOD) are associated with the pathogenesis of the familial form of amyotrophic lateral sclerosis (ALS). The clinical and pathological similarities of the familial and the sporadic forms of the disease may suggest that abnormal SOD activity takes also part in the pathogenesis of sporadic ALS. We therefore measured serum SOD activity in fifteen sporadic ALS patients. Mean serum SOD activity was 1.15 +/- 0.40 u/ml in ALS patients, 1.50 +/- 0.45 u/ml. in patients with other neurological disorders and 1.45 +/- 0.45 u/ml in.healthy controls (p < 0.021 and p < 0.031 respectively). If this sporadic ALS-related reduction in serum SOD activity will be confirmed in the diseased nervous system tissue, it may suggest that abnormal SOD activity is also associated with the motor neuron damage in the sporadic form of ALS.

The finding of oligoclonal immunoglobulin (Ig) bands in the cerebrospinal fluid (CSF) is considered a cornerstone in the diagnosis of multiple sclerosis, but can be observed in other diseases as well. In a small subset of patients only a single Ig band, confined to the CSF, is identified. We evaluated the possible diagnostic significance of such a finding. Agarose gels of 6000 CSF samples were re-examined. In 1013 samples (16.8%) there were oligoclonal bands, and in 33 additional samples (0.55%) a single band was found (without a correlating band in the serum). Full data was available for 20 single band patients. Seven patients had clinical definite multiple sclerosis. Of these, 6 had a typically prominent affective disorder and 5 had a relatively malignant course of disease. Seven additional patients had other white matter diseases of the central nervous system (CNS). The remaining patients had inflammatory diseases of peripheral nerves or CNS gray matter and non-inflammatory brain diseases. The frequency of demyelinating diseases of the CNS in patients with a single abnormal Ig band in the CSF was significantly less than in a control group of patients with oligoclonal bands. In conclusion, the finding of a single Ig band confined to the CSF may hint for a disease other than multiple sclerosis, and mark an aggressive course with affective disorder in those who do have multiple sclerosis.

Pregnant rats challenged with Bordetela Pertussis vaccine, with or without encephalitogenic antigen during pregnancy, transferred a resistance to induction of experimental autoimmune encephalomyelitis (EAE) to their offspring. Cross-fostering experiments showed that the protection against EAE is conferred during the lactation period through the transfer of anti pertussis antibodies in the milk. The degree of protection correlated with antibody levels. Passive transfer of these antibodies through intraperitoneal injection to naive adult rats also conferred the same degree of protection against EAE induction. It is suggested that such transfer of resistance and antibodies may serve as a model for the study of milk transmitted immunocompetent factors, as well as a model for the mechanisms involved in the resistance to EAE.

Human fibrotic bone marrow (BM) stroma has been shown to contain alpha-smooth muscle actin (alpha-SMA)-positive cells. These closely resemble myofibroblasts that were described in other fibrotic tissues. We studied the expression of alpha-SMA in a series of murine BM-derived stromal cell lines to investigate the cellular origin and functional significance of myofibroblast-like cells in hematopoietic tissues. Although these cell lines differed in their biologic properties, most of them expressed alpha-SMA under certain conditions. Cells expressing alpha-SMA constituted a minor population in post-confluent, growth-arrested cultures. However, the incidence of cells expressing alpha-SMA increased significantly when cultures were transferred to nonconfluent conditions. A similar increase in alpha-SMA-positive cells occurred after a strip of cells was scraped away from the confluent cell layer; the cells of the affected area acquired alpha-SMA-positive contractile phenotype. The relationship between alpha-SMA expression and hematopoietic activity was studied using a cloned cell line of BM origin (14F1.1). The ability of these endothelial-adipocyte cells to support hematopoiesis in vitro was maximal under confluent conditions, whereas their expression of alpha-SMA under such conditions was residual. Moreover, in long-term BM cultures supported by confluent 14F1.1 cells, stromal areas associated with proliferating hematopoietic precursors, known as "cobblestone areas," were devoid of alpha-SMA-positive cells. These observations suggest that the expression of alpha-SMA is reversible and inversely related to hematopoietic activity.

Anti-myelin antibodies can be found in sera from patients with neurologic disorders of suspected immune-mediated pathogenesis such as multiple sclerosis and inflammatory polyneuropathies. However, the specificity of these findings is controversial. In the present study, in vitro synthesis of antibodies to myelin components was compared to their presence in sera in diverse neurological disorders. Epstein-Barr virus was used to activate B lymphocytes for in vitro antibody production. Anti-myelin basic protein and anti-galactocerebroside antibodies were secreted in vitro by B lymphocytes derived from patients with neurological disorders of various etiologies and pathogenetic mechanisms. Anti-myelin basic protein antibodies were detected in many more cell culture supernatants than in sera from the same patients. In vitro secretion of antibodies to myelin antigens, as well as the presence of these antibodies in body fluids, are apparently non-specific for disease type and may be secondary to neural tissue damage.

Circulating autoantibodies against the acetylcholine receptor (AChR-Ab) are an important diagnostic tool in myasthenia gravis (MG). Lack of antibodies may cast doubt upon the diagnosis, the immune-mediated mechanism and the nature of the antigen. We examined clinical and laboratory features, response to immunotherapy and production of AChR-Ab in vitro, in 12 seronegative MG patients who were followed up for 2-30 years. It was possible to divide those patients into 2 groups: 7 patients with systemic muscle weakness, with a severe disease and with response to immunosuppressive therapies. The other group of 5 patients was characterized by oculobulbar symptomatology, a relatively benign course and immunotherapy was ineffective in 3 treated patients. Five patients underwent thymectomy and gland histology was normal in all of them. In none of 9 patients examined, were AChR-Ab synthesized in vitro (compared to 65% of seropositive myasthenic patients). Thus seronegative generalized MG is probably an autoimmune disease though the autoantigen is presently unknown and is responsive to immunosuppressive treatment. Seronegative oculobulbar MG might represent a separate disease entity in which immunological mechanisms play no significant role.

Activation of the immune system is believed to provide signals in the form of chemical messengers that are able to change neural activity in a variety of regions of the central nervous system. In studies designed to examine the effects of alpha-interferon (alpha-IFN) upon the central nervous system, recordings of cortical EEG were made following intracerebroventricular injection of various doses of the cytokine. Administration of 25 U of alpha-IFN increased the amount of wake and decreased the amount of desynchronized sleep in the first hour following injection; an increase in synchronization being seen in the third hour. alpha-IFN at 250 U increased the amount of synchronization and decreased the amount of desynchronized sleep in the EEG, principally in the second hour, with 2,500 U having similar but more potent effects, mostly in the first hour. The (mu) opiate receptor antagonist, naloxone, was found to decrease the amount of EEG synchronization and blocked the increases in synchronized sleep produced by 250 U alpha-IFN. The data suggest that alpha-interferon increases EEG synchronization in a dose-dependent and specific manner, probably via central mu-opiate receptors. The increased wake in the EEG following 25 U suggests, however, that another discrete effect of alpha-IFN may also exist.

We have compared the clinical signs, brain pathology and visually evoked responses (VEP) of guinea pigs with experimental allergic encephalomyelitis (EAE). Animals immunized with myelin basic protein had a milder disease, both from the clinical and histological points of views, compared to those immunized with crude white matter extract. However, VEP findings were quite similar in both groups. The VEP of the majority of animals from both groups showed changes before or at the same time that neurological signs appeared. Electrophysiological responses were usually characterized by abnormal wave shapes and prolonged latencies. Recovery of the VEP usually preceded the recovery from clinical signs. In contrast, the severity and incidence of brain tissue pathology was not correlated to either clinical signs or VEP changes. Possible explanations of the electrophysiological, clinical and histopathological changes and their time-course are discussed.

Antisera raised in rabbits against galactocerebroside bind to bovine oligodendroglia in suspension in significant titer as demonstrated by indirect immunofluorescence. Absorption of antigalactocerebroside antiserum with galactocerebroside, oligodendroglia, or myelin markedly reduces the antigalactocerebroside antibody titer as measured by a radioimmunoprecipitation test as well as the binding to oligodendroglia. Incubation with some other galactose-containing glycolipids results in a parallel decrease in binding to oligodendroglia and reduction in antigalactocerebroside antibody titer. Antigalactocerebroside antibodies provide a useful and specific tool with which to study development of oligodendroglia and myelin as well as immunopathologic mechanisms which might be involved in demyelinating diseases.

This study was designed to examine the effects of intracerebroventricular administration of a variety of immunomodulatory factors upon cortical EEG, preoptic area/anterior hypothalamic (POA/AH) multiunit activity (MUA), and corticosterone secretion in conscious, freely moving rats. The substances tested were alpha-interferon (alpha-INF), thymic humoral factor (THF), histamine, and interleukin-1 (IL-1). Saline administration did not alter POA/AH MUA up to 45 min after injection but increased the total time and duration of synchronized EEG periods. alpha-INF and THF were found to significantly reduce POA/AH MUA and increased the amount and duration of synchronized EEG while decreasing basal plasma corticosterone levels. Histamine and IL-1 did not alter POA/AH MUA discharge but decreased EEG synchronization and evoked an increase in plasma corticosterone levels. These results demonstrate that some secretions of the immune system are able to alter EEG discharge and neural activity in an area of the brain known to modulate both immune and neuroendocrine secretory activity. The results also appear to be related to adrenocortical secretory activity, which was altered by the substances tested.

Lymphocytes from patients with Bell's palsy were shown to undergo significant stimulation when cultured in vitro in the presence of a purely neuritogenic basic protein (P1L) isolated from human peripheral nerve myelin. No sensitization was observed to other neural antigens, namely, another periperal nerve myelin basic protein (P2) and the central nerve myelin basic encephalitogenic protein (BE). A similar pattern of response was also demonstrated in patients with Guillain-Barré syndrome (GBS). Lymphocytes from patients suffering from other neuropathies or other diseases involving the face showed no response to any of these antigens. The specific in vitro response to P1L protein in Bell's palsy may suggest that an in vivo sensitization of lymphocytes to such self protein occurs in this condition, and that cell-mediated, probably post-infectious, autoimmune mechanisms may be an important factor in the pathogenesis of the paralysis. Thus, Bell's palsy is immunologically similar to GBS, or may even represent a mononeuritic variant of GBS. In view of these findings the administration of steroids to patients with Bell's palsy seems logical on the basis of their immunosuppressive action.

Sera from patients with myasthenia gravis (M.G.) were studied by the quantitative micro-scale complement-fixation assay for the presence of humoral antibodies against acetylcholine receptor (AChR). The purified receptor was extracted from the electrogenic tissue of the electric ray, Torpedo californica. A significant difference in the antibody titres was observed between myasthenic and non-myasthenic patients. Out of fifteen patients with myasthenia gravis, at least 12 (80%) had antibodies against AChR. Only one case out of twenty-four controls had an indication of anti-receptor antibodies. In view of observations on the role of AChR as the autoantigen in myasthenia gravis, such antibodies may have significance in producing the neuro-muscular block characteristic of the disease.

Mechanisms by which the central nervous system may be influenced during the course of an immune response probably exist but remain obscure. In an attempt to determine any neurophysiological changes during such responses, we have employed a conscious animal model bearing chronically implanted recording electrodes in the preoptic area/anterior hypothalamus (PO/AH) and hypothalamic paraventricular nucleus (PVN). Rats were sensitized to sheep red blood cells (SRBC) injected intraperitoneally. Basal PO/AH multiunit activity (MUA) increased significantly to a maximum 5 days after SRBC injection and correlated with the initial appearance of anti-SRBC serum antibodies. Significant decreases in PO/AH MUA were recorded on Days 3 and 8 following the sensitization. PVN MUA decreased significantly for the first 3 days following immunization and then returned to a basal rate before increasing on Day 6. On the ninth and tenth days following the SRBC injection, both PO/AH and PVN MUA levels had returned to those recorded before immunization. A further group of animals was examined for PO/AH MUA changes during induction of a secondary response to SRBC. Firing rates increased significantly between Days 4 and 9 following the injection, the maximum increase being on Day 6. The profile of this response was different from that recorded during the first response, with no decreases recorded. The results are discussed in terms of neuroimmunomodulatory mechanisms such as those influencing neuroendocrine secretory function.

Myelin basic protein (MBP) was serially measured in 177 CSF samples of 33 patients with leptomeningeal metastases and in 34 cancer controls. The mean level in cancer controls (free of neural involvement) was 5.7 +/- 0.33 ng/ml (normal less than 5 ng/ml) with abnormal elevation of MBP detected in 17%. The activity of the leptomeningeal disease was classified as either acute-progressive, stable or in remission on the basis of clinical and CSF cytological findings. CSF MBP levels were analysed in each stage. Abnormal elevation of MBP was detected in 74% of the 68 samples obtained in the acute-progressive stage (mean +/- SEM: 18.25 +/- 1.4 ng/ml, P less than 0.0001), in 24% of the 79 samples in the stable phase (mean: 7.99 +/- 0.8 ng/ml, NS) and in 20% of the 30 samples in remission (mean 5.7 +/- 0.3 ng/ml, NS). Similar changes in levels of CSF MBP were also observed in longitudinal studies of patients responding to treatment or relapsing to the acute stage. Eight patients developed treatment induced necrotizing leukoencephalopathy with typical CT-scan findings; elevated levels of CSF MBP were detected in 7 of them (mean: 21 +/- 3 ng/ml) when measured within 2 weeks of diagnosis but not when measured 2 months earlier. Our study suggests that in leptomeningeal metastases, CSF MBP levels are indicators of the disease activity, particularly if longitudinal determinations are used.

Oligodendrocytes were isolated from bovine white matter and were injected with complete Freund's adjuvant (CFA) into experimental animals. Indirect immunofluorescence studies using fluoresceinated goat anti-rabbit or anti-guinea pig immunoglobulin (GARIg; GAGPIg) showed that rabbit and guinea pig anti-oligodendrocyte (RAO, GPAO) sera reacted specifically with the surface of isolated oligodendrocytes in suspension, as well as with oligodendroglia in bovine and human brain sections, and in mouse cerebellum cultures. This activity of RAO was blocked by non-fluoresceinated GARIg and by GPAO, and absorbed by oligodendrocyte preparation (OP) or whole white matter, but not by purified myelin, neuroblastoma or non-brain tissue. Low levels of anti-basic protein antibodies were found in many RAO (but not GPAO) sera by radioimmunoassay, and a few showed significant anti-galactocerebroside antibody by agglutination and radioimmunoprecipation techniques. Guinea pigs sensitized with isolated oligodendrocytes in CFA showed cell-mediated immunity (CMI) to OP as manifested by delayed type skin test and induced in vitro lymphocyte transformation. CMI to purified myelin basic protein was not detected. The demonstration of humoral and CMI to the cell responsible for the production of CNS myelin may be related to some aspects of the immunopathogenesis of demyelinating disorders.

Three patients with acute disseminated encephalomyelitis (ADE) and 4 patients in the terminal stages of multiple sclerosis (MS) were subjected to treatment with Cop 1, a synthetic copolymer of amino acids, which had previously been shown to have a beneficial effect in the treatment of experimental allergic encephalomyelitis (EAE). Under the treatment, the ADE patients recovered completely within 3 weeks, but 1 of 2 control cases treated with steroids showed complete recovery as well. The MS patients did not show any significant change in their motor function; however, 2 of them showed some improvement in vision and speech capacity. It is too early to conclude whether this improvement is related to the treatment. No side effect was observed in any of the patients treated with Cop. 1.

The effect of amniotic fluid on the binding of anti-acetylcholine receptor (anti-AChR) antibodies from myasthenia gravis (MG) patients to AChR preparations was examined by radioimmunoassay using 125I-labelled alpha-bungarotoxin. Human amniotic fluid from healthy women in their second trimester inhibited the in-vitro interaction between antibody and antigen. This finding suggests that during pregnancy there is a similar inhibitory effect in MG on the in-vivo binding of maternal anti-AChR antibodies, transferred through the placenta, to AChR at the fetal neuromuscular junction. The presence of feto-placental inhibitory factors may explain the development of transitory muscular weakness only after birth and only in the minority of the babies born to myasthenic mothers.