Faculty Bibliography

Lyme borreliosis, a tick-borne multisystem disease, may cause a variety of neurologic complications, including meningoencephalitis and encephalopathy. To evaluate neurobehavioral function following treated Lyme borreliosis, 15 patients with Lyme disease and complaints of persistent cognitive difficulty a mean of 6.7 months following antibiotic treatment underwent neuropsychological evaluation and were compared with 10 healthy controls, matched in aggregate for age and education, who underwent the identical neuropsychological assessment. Compared with controls, patients with Lyme disease exhibited marked impairment on memory tests and particularly on selective reminding measures of memory retrieval. The memory impairment did not correlate with serum or cerebrospinal fluid anti-Borrelia burgdorferi antibody titers and was not explained by magnetic resonance imaging findings or depression. The cause of this encephalopathy is currently unknown; however, indirect effects of systemic infection or other toxic-metabolic factors may be partly responsible

BACKGROUND: Psychological and immunologic factors both appear to contribute to chronic fatigue syndrome (CFS). By comparing CFS with other disorders in which fatigue is a prominent symptom, the association between fatigue, psychological vulnerability, depression, and immune function may be further defined. Recent data from psychological, neurologic, and immunologic studies that address these issues are reviewed. METHOD: Articles and abstracts covering CFS and related topics of fatigue, depression, and postinfectious syndromes were identified through MEDLINE and Index Medicus (1980-1990) and by bibliographic review of pertinent review articles. RESULTS: The 1988 definition of CFS by the Centers for Disease Control encompasses several conditions in which the major characteristic is severe fatigue associated with constitutional symptoms. Several studies have identified immune dysfunction in CFS patients, but the specificity of these findings remains unclear. Most studies have shown that CFS patients, compared with other patients with chronic medical illness, experience more disabling fatigue. Some investigators have found a higher incidence of concurrent and past psychiatric illness in CFS patients compared with other medical patients, thereby suggesting an underlying psychopathology in CFS. However, other studies have not found a higher than expected incidence of past depression in CFS patients and have further shown that many CFS patients have no identifiable psychopathology. CONCLUSION: CFS appears to be a heterogenous entity. Although there may be a high coincidence of major depression in CFS, a substantial proportion of patients lack any identifiable DSM-III-R psychiatric disorder yet still manifest the syndrome, thereby suggesting it has an autonomous entity. Despite the evolving nature of our current understanding of CFS, a rational diagnostic and therapeutic approach to CFS is possible.

We analyzed cerebrospinal fluid (CSF) from 32 patients with neurological symptoms and evidence of Borrelia burgdorferi infection (29 were seropositive as determined by enzyme-linked immunosorbent assay, 2 were cell-mediated immune positive, and 1 had been seropositive as shown by enzyme-linked immunosorbent assay 9 months previously). CSF immune complexes were found in 22 (69%) of 32 patients; in 18, there was sufficient sample to isolate immune complexes. By enzyme-linked immunosorbent assay, isolated immune complexes from 10 of these 18 patients contained antibody specific for B. burgdorferi antigens. The isotypes were IgG (n = 8), IgM (n = 3), and IgA (n = 2). By immunoblot, these antibodies were directed against B. burgdorferi 41-kDa antigen and occasionally against the 33- and 17-kDa antigens. Anti-B. burgdorferi IgM was present in patients with acute neurological symptoms, was predominantly complexed rather than free, and decreased with clinical recovery in the one serial study. Three patients were nonreactive for free CSF antibodies, but had complexed antibodies to the organism. The preliminary finding of specific B. burgdorferi components in immune complexes in CSF suggests an active process triggered by the organism, even in the absence of other CSF abnormalities.

Fifty-nine patients with systemic lupus erythematosus were evaluated by questionnaires, histories, physical examinations and routine laboratory studies in order to better understand their fatigue. The fatigue severity scale (scored from 1 to 7) was used to measure fatigue and yielded a mean score +/- SD of 4.6 +/- 1.5. Fifty-three percent of the patients reported that fatigue was their most disabling symptom. Although perceived as severe, the symptom of fatigue did not correlate significantly with any of the laboratory measures. However, there was a significant correlation between fatigue and the physician's rating of disease activity. Fatigue also correlated significantly with depression which accounted for 21% of the variation in fatigue scores.

Borrelia burgdorferi infection (Lyme disease) is frequently accompanied by CNS dysfunction. Particularly common is a mild confusional state, the mechanism of which is unknown. Since CNS infection with B burgdorferi is usually accompanied by intrathecal synthesis of specific antibody, we studied CSF in 73 patients referred for presumed CNS Lyme, manifested primarily as this confusional state. Of 30 seropositive patients evaluated, only 5 had intrathecal antibody production. Seven seronegative patients had positive cell-mediated immune responses to B burgdorferi in the peripheral blood; none had antibody production in the CSF. Of the remaining 36 patients referred with this diagnosis despite negative serologic studies, none had compelling evidence of CNS infection by this criterion. We conclude that CNS infection with B burgdorferi does occur in a small proportion of seropositive patients with this confusional state but is extremely uncommon among seronegative individuals with this clinical presentation