Chlamydia pneumoniae infection and multiple sclerosis

Possible association of Chlamydia pneumoniae and multiple sclerosis is the subject of recent interest. The findings concerning the isolation of the agent from CSF and tissue from postmortem brain are controversial, similarly as absorption of oligoclonal bands in CSF by this antigen. The hypothesis should be further studied to establish whether an association of Ch. pneumoniae with MS exists or not.     

An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis patients

We amplified sequences of the Chlamydia pneumoniae (CP) major-outer membrane protein in the cerebrospinal fluid (CSF) from 23 of 107 (21.5%) relapsing-remitting or secondary progressive multiple sclerosis (MS) patients and two of 77 (2.6%) patients with other neurological diseases (OND) (P = 0.00022). CP+ patients showed magnetic resonance imaging (MRI) evidence of more active disease (P = 0.02) compared to CP- MS patients and tended to have an anticipation of age at disease onset (32.3 +/- 12 versus 28.5 +/- 10 years; P = ns) causing a longer disease duration (7.5 +/- 5 versus 4.4 +/- 4 years; P = 0.016) at the time of clinical evaluation. These findings, although indirectly, suggest that CP infection of the central nervous system (CNS) might affect disease course in a subgroup of MS patients.     

Chlamydia pneumoniae infection of the central nervous system in multiple sclerosis

Our identification of Chlamydia pneumoniae in the cerebrospinal fluid (CSF) of a patient with multiple sclerosis (MS) led us to examine the incidence of this organism in the CSF from 17 patients with relapsing–remitting MS, 20 patients with progressive MS, and 27 patients with other neurological diseases (OND). CSF samples were examined for C pneumoniae by culture, polymerase chain reaction assays, and CSF immunoglobulin (Ig) reactivity with C pneumoniae elementary body antigens. C pneumoniae was isolated from CSF in 64% of MS patients versus 11% of OND controls. Polymerase chain reaction assays demonstrated the presence of C pneumoniae MOMP gene in the CSF of 97% of MS patients versus 18% of OND controls. Finally, 86% of MS patients had increased CSF antibodies to C pneumoniae elementary body antigens as shown by enzyme-linked immunosorbent assay absorbance values that were 3 SD greater than those seen in OND controls. The specificity of this antibody response was confirmed by western blot assays of the CSF, using elementary body antigens. Moreover, CSF isoelectric focusing followed by western blot assays revealed cationic antibodies against C pneumoniae. Infection of the central nervous system with C pneumoniae is a frequent occurrence in MS patients. Although the organism could represent the pathogenetic agent of MS, it may simply represent a secondary infection of damaged central nervous system tissue. A therapeutic trial directed at eliminating C pneumoniae from the central nervous system may provide additional information on its role in MS. Ann Neurol 1999;46:6–14     

Evidence for infection with Chlamydia pneumoniae in a subgroup of patients with multiple sclerosis

In a pilot study, we identified Chlamydia pneumoniae in the cerebrospinal fluid by polymerase chain reaction in 5 of 10 patients with definite multiple sclerosis (MS). In a second series, 2 of 20 patients with definite MS and 3 of 17 patients with possible/probable MS or MS variants, but none of 56 patients with other neurological, diseases were polymerase chain reaction-positive. We confirm that C. pneumoniae can be found in the cerebrospinal fluid of MS patients, but our rate of positive results is lower than in a recent report.     

Under the microscope: focus on Chlamydia pneumoniae infection and multiple sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) of supposed autoimmune origin whose etiology still remains unknown. Epidemiological studies suggest that MS pathogenesis could be related to an infection superimposed on a predisposing genetic background. However, at present, no direct evidence for an infectious implication in MS autoimmunity exists. Recently, the potential role of Chlamydia pneumoniae as a causative agent of MS has received increasing attention. After the initial high rates reported for molecular and culture demonstration of C. pneumoniae in cerebrospinal fluid (CSF) of MS patients, the association between C. pneumoniae and MS was intensively investigated with controversial results. Seroepidemiological reports did not show any strong association between C. pneumoniae infection and the risk of MS. Isolation techniques failed to detect C. pneumoniae in CSF and brain tissue of MS patients. Polymerase chain reaction (PCR) evidence of C. pneumoniae in CSF and intrathecal synthesis of anti-C. pneumoniae IgG have been undetectable in MS patients or, if present, were not selectively associated with MS, but were shared by several inflammatory neurological conditions. Nevertheless, in a subgroup of MS patients, an association between PCR positivity for C. pneumoniae in CSF and disease activity was found. Intrathecal production of anti-C. pneumoniae high-affinity IgG predominated in MS progressive forms and metabolically active C. pneumoniae was identified in CSF. C. pneumoniae was recognized in CSF and brain tissue at immunohistochemical, molecular and ultrastructural levels. C. pneumoniae was also able to induce the animal model of MS. This growing body of data does not support a central role for C. pneumoniae as a candidate in MS pathogenesis, but suggests that, in a subset of MS patients, C. pneumoniae could induce a chronic persistent brain infection acting as a cofactor in the development of the disease. Thus, the actual involvement of C. pneumoniae in MS still remains to be elucidated.     

Chlamydia pneumoniae infection and the risk of multiple sclerosis: a meta-analysis

We conducted a meta-analysis of studies comparing the presence of Chlamydia pneumoniae (Cpn) between multiple sclerosis (MS) patients and other neurological diseases patients or healthy controls. We identified 26 studies with 1332 MS patients and 1464 controls. Using random-effects methods, MS patients were found more likely to have detectable levels of Cpn DNA (OR = 3.216; 95% CI: 1.204, 8.585) in their cerebrospinal fluid, and intrathecally synthesized immunoglobulins (OR = 3.842; 95% CI: 1.317, 11.212), compared to other patients with neurological diseases. There is no evidence for increased levels of serum immunoglobulins (OR = 1.068; 95% CI: 0.745, 1.530), even though this result is confounded by the presence of studies using normal subjects as controls. Similarly, there is no evidence for association of immunoglobulins against Cpn in the cerebrospinal fluid (OR = 3.815; 95% CI: 0.715, 20.369). Up to 59.7% of the between-studies variability could be explained by the inappropriate matching of cases and controls for gender. In random-effects meta-regressions, adjusting for the confounding effect of gender differences results in stronger and statistically significant associations of MS with detectable levels of Cpn DNA, intrathecally synthesized immunoglobulins and immunoglobulins in the cerebrospinal fluid. Even though the presence of Cpn is clearly more likely in MS patients, these findings are insufficient to establish an etiologic relation.     

Chlamydia pneumoniae seropositivity in Iranian patients with multiple sclerosis: a pilot study

Background and purposeMultiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. Genetic and environmental factors could not completely explain the pathogenesis of the disease. Among environmental factors, infectious agents are of more interest than other candidates, so Chlamydia pneumoniae (C. pneumoniae) may have a role in MS development or progression. This study aimed to evaluate C. pneumoniae seropositivity in MS patients.Material and methodsSerum samples obtained from a cohort of 85 patients with MS and from 50 age- and sex-matched controls were assessed for the presence of antibodies. IgM and IgG concentration for C. pneumoniae were determined with enzyme-linked immunosorbent assay (ELISA).ResultsThe mean age was 33.8 (9.96) years in the MS group and 33.9 (10.7) years in controls. Female/male ratio was 3.5 : 1 in the MS group; 69 patients (81%) had relapsing-remitting course (RRMS) and 16 patients (19%) had secondary progressive course (SPMS). The median concentration of C. pneumoniae IgM in the MS group was 0.5 RU/mL (0.25–1) versus 0.5 RU/mL (0.3–0.8) in the control group (p = 0.66); likewise, the median concentration of C. pneumoniae IgG in MS patients was 57.3 RU/mL (17.05–95.1) compared with 56.15 RU/mL (6.85–102.5) in the control group (p = 0.85). Regarding the clinical course, C. pneumoniae IgG was 55.1 RU/mL (20.7–88.6) in RRMS and 59.1 RU/mL (5.35–112) in SPMS (p = 0.8).ConclusionNo association was observed between MS and C. pneumoniae in Iranian MS patients.     

Psychosis in multiple sclerosis associated with left temporal lobe lesions on serial MRI scans.

There is retrospective evidence of a correlation between psychosis in multiple sclerosis (MS) patients and temporal lobe pathology. A 35-year-old woman with MS presented with psychosis. There was no concurrent history of medication/substance use or family history. Comparison with previous MRI scans showed significant progression of lesions within the periventricular white matter of the left temporal lobe. This case highlights the association of psychosis and MS progression with worsening of left temporal lobe lesions. Prospective studies are required to ascertain the extent to which left temporal lobe lesions are predictive of future psychosis.     

Chlamydia pneumoniae and the risk for exacerbation in multiple sclerosis patients

In this prospective study of 73 relapsing remitting multiple sclerosis patients followed up for a mean of 1.7 years, the relation was tested between serologically defined Chlamydia pneumoniae (CP) infection periods and exacerbation rate. Episodes of serologically defined CP infections were observed in a subgroup, and these episodes were associated with increased risk for exacerbation. CP polymerase chain reaction was positive in most of the CP seropositive patients. No correlation was found between the anti-CP antibody increase and titers of control antibodies.     

Cerebral lymphoma associated with lesions of multiple sclerosis

A 24 year-old man experienced a left retrobulbar neuritis which improved completely after 2 months of non-steroid antiinflammatory therapy. One month after the end of the treatment he developed a Korsakoff-like amnestic syndrome. Three months later he complained of horizontal diplopia. A CT Scan showed a diffuse enhancement of the periventricular areas, corpus callosum and fornix. Diplopia and CT scan abnormalities disappeared after the administration of tetracosactide. Subsequently a progressive worsening of the neurological condition developed, including a 1 1/2 syndrome of Fisher. In C.S.F. proteins ranged from 35 to 66 mg/dl, gammaglobulins from 4 to 5 per cent, cells from 2.2 to 6.8 per mm3 without abnormal cells. Rounded areas of enhancement were observed on CT scan in pons and right occipital lobe. Usual biological tests, abdominal echography and lymphography were normal. Death occurred 15 months after the onset of symptoms. Neuropathological examination showed: 1) a cerebral lymphoma of probable B origin with distinct masses in right occipital lobe and pontine tegmentum and a more diffuse perivascular infiltration on the left side in the amygdaloid nucleus, fourth temporal gyrus, sublenticular area, hypothalamus and in the right internal capsule; 2) multiple small clear-cut foci of demyelination with myelin-axonal dissociation bilaterally in the optic pathways, periventricular regions, corona radiata, cerebral and cerebellar white matter, sublenticular areas, temporal lobes, splenium of the corpus callosum and fornices with secondary atrophy of the mamillary bodies. Both recent and old plaques were observed. Inflammatory perivascular cuffing, when present, consisted of small nontumoral lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunological time-course of gadolinium-enhancing MRI lesions in patients with multiple sclerosis

In multiple sclerosis (MS) gadolinium (Gd)-enhanced MRI activity correlates weakly with immunological markers of disease activity. We, therefore, tested the hypothesis that the poor correlation could be partly explained by the temporal profile of Gd enhancement. We measured urinary neopterin:creatinine ratios (neopt.:creat.(urine)) in 5 patients with active MS undergoing weekly Gd-enhanced MRI studies of the brain. The neopt.:creat.(urine) associated with new Gd-enhancing lesions (<8 days) was significantly higher than the ratio not associated with new Gd-enhancing lesions [mean(geometric) neopt.: creat.(urine) = 413 micromol/mol (range = 207-521) vs. 250 micromol/mol (range = 132-492), p = 0.03]. Pro-inflammatory immunological markers, which are probably produced early on in the life cycle of an active MS lesion, should preferably be correlated with newly enhancing lesions (<8 days). Failure to do this may explain the poor and unpredictable correlations between immunological markers and Gd-enhanced MRI activity, which cannot be accurately aged in cross-sectional and serial monthly MRI studies.