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C J Sindic

Publications and source records attributed to C J Sindic.

At least 37 records · Page 2Linked to original sources

Analysis of the systemic and intrathecal humoral immune response in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a subacute viral infection of oligodendrocytes by JC virus occurring almost exclusively in immunocompromised patients. By use of partially purified recombinant VP1 as antigen, the IgG response was analyzed by a quantitative ELISA of paired cerebrospinal fluid (CSF) and serum samples. An intrathecal immune response to VP1, defined as an antibody-specificity index of CSF to serum antibody titers > or =1.5, was found in 76% of PML patients (47/62) but in only 3.2% of controls (5/155) (P < .001). Intra-blood-brain barrier synthesis of VP1-specific IgG antibodies is 76% sensitive and 96.8% specific for the diagnosis of PML. Furthermore, the excellent correlation (r = .985) between the plasma cell count in brain tissue and the humoral intrathecal immune response to VP1 in PML patients suggests a role for B cells in this disorder.

Adolescent↗

Multiple sclerosis and intrathecal IgA synthesis.

A clinically definite diagnosis of multiple sclerosis was done in a 61 year-old woman who displayed severe cerebellar and pyramidal tract involvement. Symptoms developed 5 years before with unsteadiness of gait and difficulties in walking. Diagnosis was supported by evoked potentials studies and magnetic resonance imaging. However, the cerebrospinal fluid (CSF) analysis was very unusual. CSF albumin and IgG concentrations were normal, as well as the IgG index. In contrast, the IgA level and the IgA index were markedly increased and the local synthesis of IgA was estimated at 31.36 mg/l. Reduction by dithiotreitol did not change the IgA level. On affinity immunoblots, oligoclonal IgA bands were not detected but oligoclonal IgG bands were present. The strong local production of IgA in this patient seems to be therefore polyclonal.

Dithioerythritol↗

Encephalitis in immunocompetent patients due to herpes simplex virus type 1 or 2: determination by polymerase chain reaction and detection of intrathecal virus-specific oligoclonal antibodies.

Serum and cerebrospinal fluid (CSF) of 13 patients have been examined to confirm and precise the diagnosis of herpes simplex virus encephalitis (HSVE). By amplifying the DNA with a nested polymerase chain reaction (PCR), we could demonstrate the herpetic origin of these cases of encephalitis. DNA of HSV type 1 or type 2 was directly identified and differentiated, by the use of both type-specific primes in the same reaction. The primer sequences were chosen in the glycoprotein D region for HSV type 1, and in the glycoprotein G region for HSV type 2. Only one case was due to the latter. In all but one cases, an immunoaffinity-mediated capillary blotting study was also performed. This technique showed the occurrence of oligoclonal CSF-specific IgG bands, while the antigen-driven immunoblotting demonstrated intrathecal production of oligoclonal anti HSV antibodies. In most of the cases, repeated CSF analysis allowed us to study the sequential detection of viral DNA and of intrathecal synthesis of virus-specific IgG in relation to the clinical course. All the patients were treated with acyclovir. In one case, a relapse was clinically suspected, but the PCR remained negative.

Adolescent↗

The role of laboratory investigation in the diagnosis and management of patients with suspected herpes simplex encephalitis: a consensus report. The EU Concerted Action on Virus Meningitis and Encephalitis.

As effective therapies for the treatment of herpes simplex encephalitis (HSE) have become available, the virology laboratory has acquired a role of primary importance in the early diagnosis and clinical management of this condition. Several studies have shown that the polymerase chain reaction (PCR) of CSF for the detection of herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) DNA provides a reliable method for determining an aetiological diagnosis of HSE. The use of PCR in combination with the detection of a specific intrathecal antibody response to HSV currently represents the most reliable strategy for the diagnosis and monitoring of the treatment of adult patients with HSE. The use of these techniques has also led to the identification of atypical presentations of HSV infections of the nervous system and permits the investigation of patients who develop a relapse of encephalitic illness after an initial episode of HSE. A strategy for the optimal use of the investigative laboratory in the diagnosis of HSE and subsequent management decisions is described.

Acyclovir↗

The anti-Hu syndrome: a clinical and immunological study of 7 cases.

The authors describe the clinical and biological data of seven patients with anti-Hu antibodies. Six of them displayed a small cell lung carcinoma (SCLC), but no cancer was detected in the 7th patient in spite of an extensive workup. The clinical heterogeneity of the anti-Hu syndrome is emphasized. The major symptoms were linked to a severe sensory neuropathy in three cases, to cerebellitis in two cases, to dysautonomia in one case, and to gastro-intestinal pseudo-obstruction in one case. One patient also displayed EMG abnormalities characteristic of the Lambert-Eaton myasthenic syndrome. Two patients developed opsoclonus or ocular flutter associated with severe confusion in the late stage of their disease. In four patients, the neurological signs and symptoms preceded the discovery of the SCLC, and in two cases the initial detection of anti-Hu antibodies prompted the successful search for this tumor. Immunopathological events injuring the peripheral and central nervous system are briefly discussed.

Aged↗

[Tropical spastic paraparesis due to HTLV-I. 4 case reports and literature review].

We describe the clinical, radiological, neurophysiological and biological characteristics of 4 patients suffering from tropical spastic paraparesis due to a HTLV-I infection. Patient 1 immigrated in Europe at the age of 16 from Caribbean islands. Patient 2 was a White male Caucasian who lived during several years with a prostitute also native of Caribbean islands. Patient 3 was a Black male Zaïrian and Patient 4 was a female of mixed race who lived many years in Zaäire and in Senegal. All the 4 patients presented with walking difficulties, a spastic paraparesis, urinary disturbances and often, severe constipation. The diagnosis was based on a positive ELISA test for HTLV-I antibodies, confirmed in 2 cases each by Western blots and detection of the viral genome by the Polymerase Chain Reaction. In all cases, CSF pleocytosis and CSF-restricted oligoclonal IgG bands were observed. MRI of the spinal cord showed a global atrophy in 3 cases. Cerebral MRI revealed unusual extensive, progressive and symmetric lesions of the white matter in Patient 1, and some patchy periventricular lesions in Patient 4; this examination was normal in the two other cases. Sensory evoked potentials indicated abnormalities of central conduction velocities at the level of the posterior columns. The pathogenesis of tropical spastic paraparesis is briefly discussed.

Aged↗

The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients.

It is widely believed that multiple sclerosis is a T-cell mediated autoimmune disease associated with abnormalities in immunoregulation. This large, prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS patients, divided clinically into a remitting/relapsing group (n = 176) and a progressive group (n = 70), and compared their results to those of 117 healthy controls. All patients were found to have significantly elevated percentage and absolute numbers of IL2R+CD3+ cells as well as depressed percentages of CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide (CY) versus no treatment or treatment with other agents was used to group patients, dramatic declines in both percentages and absolute numbers of CD45RA+CD4+ cells were discovered. These declines were associated specifically with CY and and could be explained by this factor independent of the clinical state of the patient. The effects were seen in patients undergoing current treatment or in those exposed to CY in the near or remote past. These findings highlight the confounding effect of specific treatments on the immune profile of MS patients groups and suggest that there may be important implications for cellular function and clinical outcome in these and other patient groups.

Adult↗

The diagnosis of tuberculous meningitis.

The incidence of tuberculosis (TB) is expected to increase substantially during the next 10 years as well as its extrapulmonary manifestations, often in association with the HIV panepidemic. TB meningitis displays some clinical and radiological characteristics but the "gold standard" for diagnosis remains the identification of Mycobacterium tuberculosis in the CSF by direct staining of culture. Direct staining, however, is rarely successful and culturing of M. Tuberculosis can take 4 to 8 weeks. Other techniques may be helpful, such as the detection of an intrathecal synthesis of antimycobacterial antibodies, or the detection in the CSF of the mycobacterial genome by the polymerase chain reaction (PCR). DNA amplification, and especially the "nested" amplification protocol, may represent a major step forward and find its place as a sensitive, specific and rapid test in the routine diagnostic laboratory.

Cerebrospinal Fluid↗

Occurrence of oligoclonal IgM bands in the cerebrospinal fluid of neurological patients: an immunoaffinity-mediated capillary blot study.

We developed a highly sensitive and specific immunoaffinity-mediated capillary blot technique for the detection of oligoclonal IgM bands in CSF and sera from patients with various neurological disorders. Pre-treatment of the samples by dithiothreitol was necessary to obtain a migration of the IgM molecule into the gel of isoelectric focusing. IgM was then transferred by immunoaffinity onto a polyvinylidene difluoride sheet previously coated with anti-IgM antiserum. The limit of detection was found to be 6 ng in 15-microliters samples. The presence of CSF-restricted IgM bands was considered the result of an intrathecal synthesis and was observed in 13 out of 46 (28%) patients with MS, more frequently in acute relapses (9 out of 21, 43%), including 6 cases out of 13 presenting the first bout of the disease. Similar IgM bands were also detected in 15 out of 46 (38%) patients with CNS infections, especially in cases of neurosyphilis and neuroborreliosis. The presence of CSF oligoclonal IgM bands was linked to an increase of the IgM index in the MS group, but not in the group of infectious diseases as a whole. The occurrence of CSF-restricted oligoclonal IgM bands seems to be the most specific indicator of an intrathecal synthesis of this isotype.

Antibody Specificity↗

Polyclonal and oligoclonal IgA synthesis in the cerebrospinal fluid of neurological patients: an immunoaffinity-mediated capillary blot study.

An intrathecal synthesis of IgA has been reported in various neurological disorders. However, the frequency of its occurrence and the electrophoretic characteristics of the locally produced IgA remained a matter of controversy. We developed a sensitive immunoaffinity-mediated capillary blot technique for the detection of polyclonal and oligoclonal IgA in the CSF of 115 patients with various neurological disorders. Paired CSF and serum samples containing 50 ng IgA after appropriate dilutions were submitted to isoelectric focusing in agarose gels; IgA was then blotted onto a polyvinylidene difluoride sheet coated by an anti-IgA antiserum or by infectious antigens. The immunoblots were revealed by an alkaline phosphatase-conjugated anti-IgA antiserum. Only five samples displayed CSF-restricted oligoclonal IgA bands, including two out of 33 from MS patients. In herpetic encephalitis (n = 5) and varicella-zoster meningitis (n = 2), a strong intrathecal production of virus-specific IgA antibodies was detectable. In such cases, faint oligoclonal IgA antibodies were superimposed on a polyclonal background. A weak local production of anti-Borrelia burgdorferi IgA antibodies was present in two out of four cases of neuroborreliosis.

Adolescent↗

The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis.

A highly sensitive antigen-mediated capillary blot technique was developed for the detection of virus-specific oligoclonal IgG in paired CSF and serum samples from patients with various neurological diseases. In multiple sclerosis, intrathecal synthesis of oligoclonal antibodies was present against measles (70%), rubella (60%), varicella zoster (40%) and mumps (30%); in most cases (75%), such synthesis involved two or more viruses. In contrast, antibodies against a non-neurotropic virus (cytomegalovirus) were rarely produced in CSF from MS patients (5%). However, this 'polyspecific' reaction was not restricted to MS samples but was also observed in neurolupus and in the late phase of infectious diseases of the central nervous system. These anti-viral antibodies could be produced without de novo replication of the corresponding viral genome and are likely mere bystanders of an ongoing immune response.

Central Nervous System Diseases↗

Analysis of tuberculous meningitis cases by an immunoblotting assay based on a mycobacterial antigen complex.

Tuberculous meningitis cases were analyzed by an immunoblotting test based on Mycobacterium bovis BCG antigen complex A60. Anti-A60 immunoglobulin G (IgG) in cerebrospinal fluid (CSF) allowed early diagnosis, and concentrations decreased after recovery. In primary meningitis forms, anti-A60 IgGs were intrathecally synthesized and specific oligoclonal IgGs were present in CSF. In meningeal complications of pulmonary tuberculosis, there were matching titers of anti-A60 IgG in blood and CSF (mirror pattern). Correlation between CSF-restricted patterns and CSF pleocytosis was shown.

Adolescent↗

[Neuritis of the serratus anterior muscle associated with Borrelia burgdorferi infection].

A long thoracic nerve palsy developed in two patients with Borrelia burgdorferi infection. In both cases, pain in the shoulder preceded a scapula detachment suggesting first a diagnosis of neuralgic shoulder amyotrophia. In the first case, there was a context of typical meningoradiculitis, while the second patient had an isolated right shoulder amyotrophia without any other neurologic signs and with normal CSF analysis. A detailed anamnesis, the serology profile, and the good response to an adequate antibiotic treatment allowed us to attribute these two long thoracic nerve palsies to B. burgdorferi. This infection is important to consider as a possible etiology in cases of peripheral neuritis without other obvious causes.

Adult↗