Antibodies to Epstein-Barr virus in neurological diseases.

An association of evidence of Epstein-Barr virus (EBV) infection in 3 different cases of neurological disease not related to infectious monomucleosis is reported. A rise in antibody titres to EBV-viral capsid antigen (VCA) and early antigen (EA) in the serum and CSF was demonstrated in a patient with acute encephalitis and in a patient with a psychotic-like organic brain syndrome. Both patients demonstrated albuminocytological dissociation in the cerebrospinal fluid. IgM antibodies specific to EBV-VCA indicating a primary infection by EBV were found in both patients. In the second, concomitant infection with HSV1 probably preceding EBV infection was found. In the third patient with polyneuritis, elevated antibody titres to EBV-VCA were demonstrated. No evidence of penetration of antibodies to EBV through the blood-brain barrier, resulting from the elevated level in the serum, was demonstrated.     

Epstein-Barr virus antibodies in multiple sclerosis

Serum antibody titers to Epstein-Barr virus (EBV), an agent that persists in a latent form after the initial infection, were determined in 157 patients with multiple sclerosis and in 81 control subjects. Two patients (1.3%) and five control subjects (6.2%) lacked antibodies to EBV. In the subjects with antibodies, the prevalence of high titers (greater than or equal to 1:160) was significantly greater in patients, 69 (44.5%), than in control subjects, 22 (28.9%). The geometric mean titer of antibodies to EBV was significantly higher in patients, 107.0, than in control subjects, 77.1. There was no association between antibody titers and duration or activity of the disease. These findings further support the contention that patients with multiple sclerosis have a general aberration of the immunological system.     

Influenza virus and neurological diseases

Abstract  Influenza viruses rarely cause acute encephalopathy. Post-influenzal encephalitis, which occurs a few weeks after recovery from influenza is thought to be an autoimmune process associated with demyelination and vasculopathy. It has been suggested that Economo lethargic encephalitis followed by postencephalitic Parkinsonism was associated with the influenza A epidemic of 1918 (Spanish flu). The incidence of Reye's syndrome has markedly decreased due to the avoidance of salicylates in the treatment of influenza or varicella. One inactivated flu vaccine is thought to have caused Guillain Bane syndrome due to molecular mimicry between viral protein and myelin, which triggered autoimmune responses. The persistence of influenza virus genes in neural cells as one of the causes of chronic degenerative diseases of the central nervous system by inducing apoptosis of the host cells is yet to be proven.     

Cold reactive antilymphocyte antibodies in neurological diseases.

Cold reactive (15 degrees C) antilymphocyte antibodies were detected in the sera of 33% of patients with multiple sclerosis, 50% with Guillain-Barré syndrome, 42% with myasthenia gravis, and 38% with polymyositis. We did not detect such antibodies against autologous cells in multiple sclerosis. In multiple sclerosis there was no correlation between the presence of antilymphocytic antibodies and disease activity or duration. In patients with multiple sclerosis, myasthenia gravis, and polymyositis there was no correlation between the presence of cold reactive antilymphocyte antibodies and abnormalities of T or B cell levels.     

Serum IgG and IgM anticardiolipin antibodies in neurological diseases

To determine whether anti-cardiolipin antibodies (ACA) are associated with multiple sclerosis (MS) or myasthenia gravis (MG), sera from 42 patients suffering from MS and from 21 patients with myasthenia were studied, using an enzyme-linked immunosorbent assay (ELISA). No significant difference in IgG or IgM immunoglobulin isotypes between the MS myasthenic patients and controls was found.     

Anticardiolipin antibodies in patients with rabies vaccination induced neurological complications and other neurological diseases

We reported the occurrence of anticardiolipin antibodies (ACA) by using an enzyme-linked immunosorbent assay (ELISA) in sera of patients with neurologic complications from Semple rabies vaccination. There was a correlation between the presence of ACA and the disease severity. Sixteen of 25 patients (64%) with major neurological complications, 2 of 21 patients (10%) with minor complications, and non of the normal vaccinees had an ACA response. In comparison to this, ACA was found in 10/43 (24%) of patients with post-infectious encephalitis (PIE), Guillain-Barré syndrome (GBS) and multiple sclerosis (MS), 5/22 (23%) and 4/31 (13%) of patients with degenerative neurological diseases and central nervous system (CNS) infections, respectively. There was no specific restriction to any particular isotype. Frequency difference of ACA responses was unremarkable in systemic lupus erythematosus (SLE) patients with (3/9) and without (3/10) CNS involvement. It is not conclusive about the pathogenetic role of ACA. This remains to be determined.     

Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases

OBJECTIVE: Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid into GABA. GAD autoantibodies (GAD-Ab) have been described in diabetes mellitus and in diseases involving the central nervous system such as stiff-person syndrome and cerebellar ataxia. However, the pathogenic role of GAD-Ab in neurological diseases remains a matter of debate. METHODS: Using neurophysiological and neurochemical methods, we analyzed the effects of intracerebellar and paraspinal administration of GAD-Ab in rats. RESULTS: Intracerebellar administration of IgG from patients with GAD-Ab and neurological involvement (IgG-GAD) blocked the potentiation of the corticomotor response normally associated with trains of repetitive peripheral nerve stimulation. When injected in the lumbar paraspinal region, IgG-GAD induced continuous motor activity with repetitive discharges, abnormal exteroceptive reflexes, and increased excitability of anterior horn neurons, as assessed by F/M ratios. Furthermore, IgG-GAD significantly reduced the N-methyl-D-aspartate-mediated production of nitric oxide in cerebellar nuclei and impaired the synaptic regulation of glutamate after N-methyl-D-aspartate administration. These effects were not observed after administration of IgG from the following groups: (1) patients with GAD-Ab, diabetes mellitus, and without neurological complications; and (2) control patients. INTERPRETATION: These results indicate that stiff-person syndrome and cerebellar ataxia are the direct consequence of antibody-mediated neuronal dysfunction.     

Serum antibodies to Epstein-Barr virus in patients with major depressive disorder

To determine whether major depressive disorder might be associated with serologic evidence for a chronic active Epstein-Barr virus infection, viral-specific antibodies were measured in two separate groups of depressed patients (N=43) and in 46 appropriately matched healthy volunteers. No evidence that depression affects cellular immunity to the point that a persistent Epstein-Barr virus carrier state becomes activated was found. There was also no evidence that depression results from an unrecognized chronic active Epstein-Barr virus infection. The authors conclude that the routine clinical determination of expensive commercial Epstein-Barr virus antibody profiles is not indicated in most patients with major depressive disorder in the absence of other signs of chronic active Epstein-Barr viral infection.     

Monoclonal antibodies against Epstein-Barr virus cross-react with alpha-synuclein in human brain

Using antibodies generated against the latent membrane protein 1 of Epstein-Barr virus, intense immunoreactivity of Lewy bodies (in PD and dementia with Lewy bodies) and glial cytoplasmic inclusions (in multiple system atrophy) was demonstrated. ELISA and Western blotting techniques confirmed that this immunolabeling was due to cross-reactivity of the antiviral antibody with alpha-synuclein, a neuronal protein implicated in the pathogenesis of PD. This example of cross-reactivity between Epstein-Barr virus and alpha-synuclein may bear implications for further elucidating infectious or autoimmune mechanisms in PD.     

Human T-cell lymphotropic virus type I and neurological diseases

Human T-cell lymphotropic virus type I (HTLV-I) infection is associated with a variety of human diseases. In particular, there are two major diseases caused by HTLV-I infection. One is an aggressive neoplastic disease called adult T-cell leukemia (ATL), and another is a chronic progressive inflammatory neurological disease called HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is still unknown why one virus causes these different diseases. With regard to HAM/TSP, virus-host immunological interactions are an considered to be important cause of this disease. Coexisting high HTLV-I proviral load and HTLV-I-specific T cells (CD4+ T cells and CD8+ T cells) is an important feature of HAM/TSP. Histopathological studies indicate the existence of an inflammatory reaction and HTLV-I-infected cells in the affected lesions of HAM/TSP. Therefore, the immune response to HTLV-I probably contributes to the inflammatory process of the central nervous system lesions in HAM/TSP patients.     

Age-specific prevalence of Epstein-Barr virus antibodies in adult patients with affective disorders

It has been suggested that prior Epstein-Barr virus (EBV) infection is a necessary condition for the development of affective disorders. To address this issue, the authors performed serologic screening for the presence of EBV antibodies in 60 adult patients seen at an affective disorders investigational unit. Six patients with clinically significant mood disorders, all aged 32 years or younger, had no detectable EBV antibodies. The authors conclude that the onset of clinical mood disorders can occur before primary EBV infection; thus, EBV infection is not a necessary condition for the development of mood disorders.     

Cerebrospinal BAFF and Epstein-Barr virus-specific oligoclonal bands in multiple sclerosis and other inflammatory demyelinating neurological diseases

We measured circulating serum and cerebrospinal fluid (CSF) concentrations of B lymphocyte activating factor of the tumour necrosis factor superfamily (BAFF), and determined total and Epstein-Barr virus (EBV)-specific oligoclonal IgG bands (OCBs) in 43 patients with multiple sclerosis (MS), 23 patients with other inflammatory demyelinating neurological diseases, and 20 patients with non-inflammatory neurological diseases. Serum and CSF BAFF concentrations did not differ in the three studied groups. In MS, the highest BAFF concentrations were found in the CSF samples with more than 6 OCBs (233.1 ± 129.5 vs 79.2 ± 51.6 pg/mL in the samples with less than 7 OCBs, p<0.0001). Irrespectively from BAFF levels, EBV-specific OCBs were detected in MS and in the other non-inflammatory and inflammatory demyelinating neurological diseases, with a similar frequency, and as a 'mirror pattern' in 30 of 33 EBV-specific OCB-positive cases (p<0.0001). These results indicate that circulating CSF BAFF concentrations cannot help differentiate MS from other inflammatory demyelinating neurological diseases, but positively associates with the qualitative expression of elevated intrathecal IgG production in MS, and that the oligoclonal EBV-specific antibody response, when present, is mostly systemic in all the studied neurological patients, and not preferentially restricted to MS.     

Constipation in neurological diseases

Hippocrates noted that "it is a general rule, that intestines become sluggish with age", though the precise mechanisms for this association remains uncertain even today.     

Laryngospasm in neurological diseases

Laryngospasm is a clinical symptom characterized by involuntary spasms of the laryngeal muscles, which leads to paroxysms of coughing, inspiratory stridor, and sometimes to episodes of complete upper-airway occlusion. Although laryngospasm is a symptom mainly seen in otolaryngeal diseases and in the context of anesthesiological complications, it also occurs in neurological disorders. In this review of the occurrence of laryngospasms in neurological diseases, the clinical symptomatology, additional circumstances, possible underlying causes, and therapeutic options are presented.     

Insomnia in neurological diseases

Insomnia is the most common sleep complaint. Insomnia is not a disease itself but mostly a clinical sign of an underlying disease. Degenerative and vascular diseases involving the central nervous system (CNS) may impair sleep either as a result of the brain lesion or because of illness-related discomfort (motor immobility, social and familial impairment, depression, drugs). Some neurological conditions characterized by movement disorders that start or persist during sleep hinder sleep onset and/or sleep continuity, causing a poor sleep complaint. CNS lesions and/or dysfunction in three specific neurological conditions (fatal familial insomnia, Morvan's chorea, and delirium tremens) impair the basic mechanisms of sleep generation inducing a syndrome in which the inability to sleep is consistently associated with motor and sympathergic overactivation. Agrypnia excitata is the term that aptly defines this generalized overactivation syndrome.     

Increased prevalence and titer of Epstein-Barr virus antibodies in patients with multiple sclerosis

The prevalence and titer of serum antibodies to several Epstein-Barr virus (EBV) antigens were compared among patients with multiple sclerosis, healthy siblings of multiple sclerosis patients, patients with other neurological diseases, and healthy non-blood-related subjects. Serum-cerebrospinal fluid (serum-CSF) pairs were available on a selected number of multiple sclerosis and control subjects. An increased antibody response to EBV antigens was noted rather consistently in the sera of the multiple sclerosis group in comparison with the control groups. A greater number of reduced ratios of serum:CSF IgG antibody to EBV-capsid antigen and antibody to EBV-early antigen components than to adenovirus, a reference or control virus, were found in the multiple sclerosis group. Reduced ratios of these EBV antibodies were detected more frequently or showed a trend in this direction in multiple sclerosis patients compared with the group with other neurological diseases. Our findings extend the results of an earlier report and strengthen the association between EBV and multiple sclerosis.