CSF analysis in multiple sclerosis.
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Biomedical subjects
Publications and source records attributed to C J Sindic.
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Soluble interleukin-2 receptors (sIL-2-R) were determined longitudinally in sera from 59 patients with multiple sclerosis (MS), from 20 patients with Guillain-Barré syndrome (GBS) and from patients with other non-inflammatory disorders of the nervous system, as well as in 147 CSF samples collected for diagnostic purposes. Significantly increased serum levels of sIL2-R were observed early in the course of GBS and in progressive (relapsing or chronic) MS, but not in patients with clinically stable MS or with an acute relapse followed by complete remission. CSF levels were high in infections of the central nervous system and in meningeal carcinomatosis, as a result of an intrathecal production, but were normal in GBS and in most (94%) MS patients.
A 21-year-old woman developed hyperemesis gravidarum, complicated by Wernicke's encephalopathy and central pontine myelinolysis. For the latter, time course of the lesions on magnetic resonance imaging suggests a pathogenetic role for hypophosphatemia rather than for hyponatremia.
The serum and CSF of two women with a severe subacute pancerebellar syndrome contained high titers of antibodies directed against antigens present in the perikaryon of Purkinje cells. In Western blots performed on human Purkinje cells extracts these antibodies reacted with two groups of proteins the molecular weights of which were estimated to 34-38 and 62 kilodaltons (anti-Yo antibodies). Complementary investigations revealed a tubar adenocarcinoma in the first case, an ovarian carcinoma in the second. The tubar tumoral cells also contained the protein of the highest molecular weight. Compared to the serum, the CSF contained a higher proportion of anti-Yo antibodies per mg IgG, and a fraction of the latter was likely synthesized intrathecally. These antibodies may be involved in the almost total disappearance of the Purkinje cells, as observed at autopsy of both cases.
As beta-2 transferrin is almost specific to the cerebrospinal fluid, its detection in rhinorrhea or otorrhea fluids demonstrates the occurrence of CSF fistula. We describe a highly sensitive method based on immunoaffinity-mediated capillary blotting for the detection of this cathodic isoform of transferrin in minute amounts (3 microliters) of rhinorrhea or otorrhea fluids. Application of this method in a series of 10 patients with CSF fistula is reported.
We retrospectively reviewed the clinical files of 45 Guillain-Barré syndrome (GBS) patients admitted to our Department between 1979 and 1989. The age distribution was bimodal with a first peak in young adults (20-40 years), and a second one between 60 to 70 years. Seasonal distribution showed a late fall and a hivernal predominance. Three patients experienced a second attack of GBS 2-9 years after the first one. Thirty-one (69%) presented antecedent events, most often a respiratory tract infection (n = 20) or enteritis (n = 6). Serological studies were systematically performed, including antibody titers against herpes simplex virus, Epstein-Barr virus, cytomegalovirus (CMV), respiratory syncytial virus, human immunodeficiency virus, Mycoplasma pneumoniae, Campylobacter jejuni/coli and cardiolipin. These studies showed the presence of antibodies indicative of a CMV primary infection in 22% cases and of a Campylobacter jejuni/coli infection in 13%. Co-infection was observed in 3 cases. Serology remained negative in 12 patients with a preceding respiratory infection. There was no correlation between serology and the severity of the disease. Absence of antecedent events and of positive anti-infectious serology was observed in only 10 patients.
We describe an affinity-mediated capillary blotting technique for the detection of free kappa or lambda light chains in native cerebrospinal fluid (CSF) after isoelectric focusing in agarose gel. Interferences by light chains bound to immunoglobulins were carefully excluded. An absolute amount of 20-50 ng of free kappa or lambda Bence-Jones proteins were detectable by this method, under the form of several discrete bands with isoelectric points between 5 and 8.5. No free light chains were observed in CSF and sera from patients without neurological disorders (n = 26). Such bands were present in most CSF samples in the case of central nervous system (CNS) infections, except in aseptic meningitis. In a group of 48 multiple sclerosis (MS) patients, 44 (92%) displayed oligoclonal free kappa bands restricted to the CSF; oligoclonal IgG bands were observed in 40 cases, and oligoclonal free lambda bands in 33. In this group, the presence of CSF free light chain bands was highly correlated with their absolute levels (p less than 0.001). In other neurological diseases (n = 44), oligoclonal free kappa and free lambda bands were detected much more rarely, in seven (16%) and four (9%) cases respectively. Surprisingly, the CSF from three unrelated patients with Huntington's disease (out of five tested) contained both oligoclonal IgG and free kappa bands.
The authors report a case of compression of the peroneal nerve by an intraneural ganglionic cyst. The chief complaint is generally a lateral upper leg pain occasionally associated with foot drop and swelling of the upper tibiofibular joint. In our case, the disease was revealed by a tentative intraarticular injection of betamethasone. Early microsurgical treatment remains the only way to avoid permanent motor sequellae.
A case of Streptococcus suis meningitis is observed in a 39-year-old and previously healthy meat factory worker. Neurological recovery was incomplete despite adequate and sustained antimicrobial therapy. Early deafness was demonstrated by brainstem auditory evoked potentials. Death due to aspiration pneumonia, cardiac arrest and subsequent cerebral anoxia occurred late in the course of the illness.
Two sexually active female patients presented with acute meningitis. The CSF abnormalities were severe and persistent. In spite of the absence of genital lesions, serological studies revealed a primary infection by herpes simplex virus type 2. An immunoblot study revealed intrathecal synthesis of anti-herpes antibodies early in the course of the disease.
Cerebrospinal fluid (CSF) and serum samples from eight patients with bacteriologically proven (6) or clinically suspected (2) tuberculous meningitis were tested for the presence of anti-mycobacterial IgG antibodies by an affinity-mediated immunoblot technique. This technique is based on agarose gel isoelectric focusing of paired CSF and serum samples diluted to the same IgG concentration, and transfer of the specific IgG antibodies onto mycobacterial antigen-loaded nitrocellulose sheets. An intrathecal synthesis of anti-mycobacterial oligoclonal IgG antibodies, often superimposed on diffuse polyclonal production was shown in all patients but not in patients with tension headache or other neurological disorders. Similar results were obtained when a purified mycobacterial antigen, A60, was used for coating the nitrocellulose sheets in place of a whole mycobacterial homogenate, indicating that A60 was a major immunogen. The number of anti-mycobacterial oligoclonal IgG bands increased with time, and persisted for years even in clinically cured patients. Some IgG bands had no detectable anti-mycobacterial activity, at least with the antigens preparations used in this study. The demonstration of such anti-mycobacterial IgG bands in the CSF could be a useful adjunct for the diagnosis of tuberculous meningitis, especially in the case of negative cultures.
We report four patients with Behçet's disease characterized by initial and predominant neurological signs and symptoms. In three cases, a clinical picture of relapsing meningoencephalitis preceded the appearance of the classical signs of the disease for several months or years; in the fourth case, an acute febrile aseptic meningitis coincided with the development of bipolar aphthosis and uveitis. Disease activity was linked to a blood inflammatory syndrome and neutrophilic leucocytosis. Acute phases were associated with CSF mixed pleocytosis and high protein content. Brain CT scans and MRI were very effective to detect lesions which are mainly located in the brain stem and basal ganglia. High-dose corticosteroids and, in cases of relapses, immunosuppressive drugs were required to treat these severe forms of Behçet's disease.
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We present a sero-epidemiological study of 190 Belgian cases of Lyme borreliosis, a multisystemic disease caused by the spirochaete Borrelia burgdorferi and transmitted by a tick bite. The whole spectrum of clinical pictures was observed in these patients, including "erythema chronicum migrans" (63%), neurological involvement (47%) and arthritis (22%), frequently in combination. Our results are compared to findings in other countries. Among the 437 Ixodes ricinus ticks collected in the Sambre and Meuse valleys around Namur, we discovered 43 ticks (9.8%) with spirochaetes in the midgut. The ecology of these arthropods explains why this infection is more prevalent in the spring and the summer. Perhaps for the same reason, the incidence ranges from low near the coast to medium in the central part and high in the wooded south-eastern part of Belgium. The main conclusions are that Lyme borreliosis is endemic in Belgium, that all the clinical pictures can be observed ant that a clear epidemiological case-definition is needed, combining clinical signs and serological results.
Sensory subacute neuropathies associated with sicca syndrome without any systemic involvement have been reported rarely. A sixth case is described with what appears to be the first report of muscle and nerve biopsy findings. The histological studies revealed axonal degeneration without vasculitis in the sural nerve, and a slight denervation process and a discrete myositis in the gastrocnemius muscle, reflecting a subtle systemic disorder. The clinical course of a long-standing subacute sensory neuropathy, the biopsy-documented axonal degeneration, and the neurophysiological findings suggest involvement of the dorsal root ganglia.
Free kappa and lambda light chains were assayed by particle-counting immunoassay in cerebrospinal fluid (CSF) from patients with various neurological disorders. Detection limits were 25 and 50 ng/ml, respectively. Values of free kappa chain were higher than 50 ng/ml (upper reference limit) in 155 of 191 (81%) multiple sclerosis (MS) patients, in 100 of 168 (60%) patients with central nervous system (CNS) infections but in 41 of 217 (19%) patients with other neurological disorders. Free kappa chains were also assayed in 273 matched sera. The mean concentration in the control group (1.58 micrograms/ml; SD: 0.41) did not differ significantly from those in MS sera (1.63 micrograms/ml; SD: 0.43). The free kappa chain index was increased in 86% of MS patients and in 40% of patients with CNS infections. Regarding free lambda chains, CSF values were higher than 240 ng/ml (upper reference limit) in most neurological disorders (50-100%). However, the use of a lambda chain index increased the specificity of the assay as this index was higher than the upper reference value in 86% of MS patients and in only 23% of patients with infectious diseases. In MS, high levels of free kappa and lambda indices correlated significantly (P less than 0.01) with either the presence of oligoclonal bands or a high IgG index. Local synthesis of free light chains is an additional marker of an ongoing immune response within the CNS, especially in MS.
Sequential measurements of brain glucose metabolism were carried out in a patient with Wilson's disease, before and after successful treatment with D-penicillamine. They demonstrate an evolution of regional metabolism consistent with clinical improvement. The first study showed marked hypometabolism in the putamen on both sides. The second analysis showed bilateral improvement, with predominant residual deficits in the right putamen, while clinical symptoms of striatal dysfunction persisted on the left side. This observation suggests that positron emission tomography is able to follow the neurological evolution in cases of Wilson's disease.
CSF and serum samples from 16 AIDS patients were tested for the presence of anti-HIV antibodies either by classical serological methods or by an immunoblot technique based on agarose gel isoelectric focusing and transfer of the specific IgG antibodies onto HIV antigens-loaded nitrocellulose sheets. This method enabled the demonstration of an intrathecal synthesis of anti-HIV oligoclonal IgG antibodies, often superimposed on diffuse polyclonal production, in 14 patients. The two negative cases were devoid of neurological signs or symptoms. However, two patients classified in stage II of the disease (asymptomatic infection) displayed an intrathecal synthesis of anti-HIV antibodies.