Postlyme Disease Syndrome

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The terms post-Lyme disease syndrome and post-treatment chronic Lyme disease are used to describe patients who were previously diagnosed with Lyme disease and develop persistent encephalopathic symptoms months to years after antibiotic treatment. Not all patients with a clinical history of Lyme disease who later present with encephalopathic symptoms are seropositive or have abnormal CSF. Most patients who are seronegative do not have Lyme disease, although it is possible to be seronegative and have post-Lyme syndrome. There are also reported cases of seronegative patients with CSF evidence of Lyme infection; however, this is rare. Most patients diagnosed with post-Lyme syndrome are seropositive for Lyme disease and develop symptoms after treatment.

In 1991, Krupp and colleagues compared a group of treated Lyme disease patients who continued to report memory problems after treatment, to a group of healthy controls. All subjects received a similar neuropsychological test battery to those described previously, with the addition of a fatigue rating scale. There were no differences between patients and controls on the any of the intelligence tests, tests of tracking and sequencing, and tests of abstract problems solving. The Lyme disease group performed significantly worse on the verbal fluency and two memory measures. Patients were also more depressed than controls. Neuropsychological test scores remained lower in the Lyme group, relative to controls, even when the presence of depression was controlled

LTS cLTR

Figure 5 A comparison of memory scores for patients with LE, post-Lyme disease syndrome (PLS), and normal controls on the Selected Reminding Test. The two measures compared are total words recalled (LTS) and consistency of recall (cLTR).

statistically. Impairment was greatest for word recall on a verbal list learning test, the Selective Reminding Test (SRT). However, recognition memory did not discriminate patients and controls. The Lyme patients were also divided by the severity of neuropsychological impairment into mild, moderate, or severe categories based on the number of tests in which a patient's score fell below the published normative means (one or two standard deviations). On this basis, 9 of the 15 patients showed evidence of mild to moderate cognitive impairment, whereas 6 patients appeared normal despite complaints of memory trouble. Neither evidence of CSF infection nor MRI abnormalities correlated with the degree of cognitive impairment. However, fatigue was correlated with memory performance in the Lyme group but not the control group, with higher levels of fatigue associated with greater memory impairment. Interestingly, depressive symptoms were also correlated with memory scores. Par-odoxically, however, more depressive symptoms corresponded to better memory scores.

Because it appeared that cognitive deficits exist in some Lyme patients independent of other evidence of neurological involvement, my colleagues and I studied the relationship between active infection and cognitive dysfunction. We compared 13 seropositive Lyme patients with evidence of inflammatory CSF to 20 seropositive Lyme patients without evidence of neu rological disease and 14 age-matched normal controls. Most patients in both Lyme groups described memory deficits as one of their symptoms. Eleven of 13 patients with abnormal CSF and 16 of 20 with normal CSF reported memory problems, versus none of the controls. On the SRT verbal memory measure, Lyme patients with abnormal CSF recalled significantly fewer words, were less consistent in their recall, and retrieved fewer items from memory than either Lyme patients with normal CSF or normal controls, who did not differ on any of these measures (Fig. 5). On the BDI, both Lyme disease groups endorsed significantly more symptoms than the normal control group, although no group's score was sufficiently high to meet the criteria for depression. Thus, although both groups of Lyme reported memory difficulties in our study, only the group with evidence of CNS infection performed more poorly on objective memory testing. However, both Lyme groups reported more symptoms of depression and anxiety than healthy controls (Fig. 6). These data suggest that depression may be a factor in perceived memory loss.

As a group, Lyme patients report significantly more symptoms of depression and fatigue than do controls, independent of evidence of CNS disease. In several studies the average depression scores for the Lyme patients were typically higher than for healthy controls but below the suggested cutoffs for clinical depression.

Beck Depression Inventory State-Trait Anxiety Scale

Beck Depression Inventory State-Trait Anxiety Scale

Figure 6 Depression and anxiety for LE, post-Lyme disease syndrome (PLS), and normal controls.

Figure 6 Depression and anxiety for LE, post-Lyme disease syndrome (PLS), and normal controls.

Moreover, although a significant proportion of Lyme patients meet the criteria for depression, depression scores and objective measures of memory loss have not been highly correlated. Fatigue, however, has been shown to be significantly correlated with poor memory in a number of studies.

In the study described previously, most Lyme patients complained of memory disturbance whether or not they had abnormal CSF. As such, the perception of memory loss was not a good predictor of objective impairment on neuropsychological testing. This finding has been replicated in several studies of Lyme disease patients. It is also not unique to Lyme disease. In most studies, self-reported poor memory is only weakly related to actual memory test performance, whereas it is strongly associated with conventional affective symptoms. Most studies have been done with elderly patients. These have shown that the relationship between subjective estimates of memory loss and objective measures of memory impairment is low. Instead, perceived memory loss tends to be related to psychological distress. As with many chronic illnesses, Lyme patients with late-stage disease often experience greater emotional distress, including depression and anxiety, than otherwise healthy people, although they do not meet the clinical criteria for psychopathology. It is therefore likely that the perceived memory disturbance in many Lyme patients may be related to the stress and affective symptoms common to many chronic diseases.

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Getting to Know Anxiety

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