Retrograde and semantic amnesia in a case of post-treatment Lyme disease syndrome: did something lead to a psychogenic memory loss? A single-case study.

OBJECTIVE: To describe a case of Post-Treatment Lyme Disease Syndrome (PTLDS) with an atypical cognitive profile. METHOD: A 41-year-old PTLDS patient underwent comprehensive neuropsychological testing and psychological assessment. RESULTS: The patient exhibited impaired intensive attention but preserved selective attention. Executive functions were normal. Short-term and anterograde memory were intact, while retrograde and semantic memory were significantly impaired. The patient also experienced identity loss, specific phobias, dissociative symptoms, and depressed mood. CONCLUSIONS: Severe episodic-autobiographical and retrograde semantic amnesia was consistent with some reports of dissociative amnesia. Loss of identity and phobias were also highly suggestive of a psychogenic mechanism underlying amnesia.

Non-specific symptoms and post-treatment Lyme disease syndrome in patients with Lyme borreliosis: a prospective cohort study in Belgium (2016-2020).

BACKGROUND: Patients with Lyme borreliosis (LB) may report persisting non-specific symptoms such as fatigue, widespread musculoskeletal pain or cognitive difficulties. When present for more than 6 months and causing a reduction in daily activities, this is often referred to as post-treatment Lyme disease syndrome (PTLDS). This study aimed to compare the occurrence of symptoms between LB patients and controls, to estimate the proportion of LB patients developing PTLDS and to identify risk factors. METHODS: A prospective cohort study was set up including three subpopulations: patients with an erythema migrans (EM) (i) or disseminated/late LB (ii) and a non-LB control group (iii). At 6- and 12-months follow-up, the occurrence of several symptoms, including six symptoms used to define PTLDS, i.e. muscle pain, joint pain, fatigue, memory problems, difficulties concentrating and problems finding words, and impact on daily activities, was compared between LB patients and controls. Finally, the proportion of LB patients developing PTLDS as defined by the Infectious Disease Society of America was estimated, including a time frame for symptoms to be present. RESULTS: Although the risk of presenting PTLDS-related symptoms was significantly higher in EM patients (n = 120) compared to controls (n = 128) at 6 months follow-up, the risk of presenting at least one of these symptoms combined with impact on daily activities was not significantly higher in EM patients, at either 6- or 12-months follow-up. A significant association was found between disseminated/late LB (n = 15) and the occurrence of any PTLDS-symptom with an impact on daily activities at both time points. The proportion of patients with PTLDS was estimated at 5.9% (95% CI 2.7-12.9) in EM patients and 20.9% (95% CI 6.8-64.4) in patients with disseminated/late LB (RR = 3.53, 95% CI 0.98-12.68, p = 0.053). No significant risk factors were identified, which may be explained by small sample sizes. CONCLUSIONS: In our study, PTLDS was present in both LB cohorts, yet with a higher percentage in disseminated/late LB patients. Additional research is needed into risk factors for and causes of this syndrome. In addition, development and validation of standardized methods to assess the PTLDS case definition, easily applicable in practice, is of great importance.

Language Fluency Deficits in Post-treatment Lyme Disease Syndrome.

OBJECTIVE: Recent neurocognitive studies of patients with post-treatment Lyme disease syndrome (PTLDS) find consistent deficits in memory and processing speed. Language fluency deficits are observed as well but may be secondary to poor memory and slowing rather than an independent deficit. METHOD: This study performed a secondary analysis of data presented previously, including individuals with PTLDS and comparison samples of healthy volunteers (HC) and patients with major depressive disorder (MDD), to determine if language fluency deficits could be accounted for by poor performance in these other neurocognitive domains. RESULTS: Basic verbal abilities, memory, and processing speed were all significantly associated with fluency performance. MDD patients' fluency deficits relative to HC were accounted for by these covariates. However, PTLDS patients' poorer fluency performance relative to both other groups was not. CONCLUSIONS: Language fluency appears to be an independent area of neurocognitive deficit within the constellation of PTLDS symptoms.

Systematic comparisons between Lyme disease and post-treatment Lyme disease syndrome in the U.S. with administrative claims data.

BACKGROUND: Post-treatment Lyme disease syndrome (PTLDS) is used to describe Lyme disease patients who have the infection cleared by antibiotic but then experienced persisting symptoms of pain, fatigue, or cognitive impairment. Currently, little is known about the cause or epidemiology of PTLDS. METHODS: We conducted a data-driven study with a large nationwide administrative dataset, which consists of more than 98 billion billing and 1.4 billion prescription records between 2008 and 2016, to identify unique aspects of PTLDS that could have diagnostic and etiologic values. We defined PTLDS based on its symptomatology and compared the demographic, longitudinal changes of comorbidity, and antibiotic prescriptions between patients who have Lyme with absence of prolonged symptoms (APS) and PTLDS. FINDINGS: The age and temporal distributions were similar between Lyme APS and PTLDS. The PTLDS-to-Lyme APS case ratio was 3.42%. The co-occurrence of 3 out of 19 chronic conditions were significantly higher in PTLDS versus Lyme APS-odds ratio and 95% CI for anemia, hyperlipidemia, and osteoarthrosis were 1.46 (1.11-1.92), 1.39 (1.15-1.68), and 1.62 (1.23-2.12) respectively. We did not find significant differences between PTLDS and Lyme APS for the number of types of antibiotics prescribed (incidence rate ratio = 1.009, p = 0.90) and for the prescription of each of the five antibiotics (FDR adjusted p values 0.72-0.95). INTERPRETATION: PTLDS cases have more codes corresponding to anemia, hyperlipidemia, and osteoarthrosis compared to Lyme APS. Our finding of hyperlipidemia is consistent with a dysregulation of fat metabolism reported by other researchers, and further investigation should be conducted to understand the potential biological relationship between the two. FUNDING: Steven & Alexandra Cohen Foundation, Global Lyme Alliance, and the Pazala Foundation; National Institutes of Health R01ES032470.

A Review of Post-treatment Lyme Disease Syndrome and Chronic Lyme Disease for the Practicing Immunologist.

Lyme disease is an infection caused by Borrelia burgdorferi sensu lato, which is transmitted to humans through the bite of an infected Ixodes tick. The majority of patients recover without complications with antibiotic therapy. However, for a minority of patients, accompanying non-specific symptoms can persist for months following completion of therapy. The constellation of symptoms such as fatigue, cognitive dysfunction, and musculoskeletal pain that persist beyond 6 months and are associated with disability have been termed post-treatment Lyme disease syndrome (PTLDS), a subset of a broader term "chronic Lyme disease." Chronic Lyme disease is a broad, vaguely defined term that is used to describe patients with non-specific symptoms that are attributed to a presumed persistent Borrelia burgdorferi infection in patients who may or may not have evidence of either previous or current Lyme disease. The diagnoses of chronic Lyme disease and of PTLDS have become increasingly relevant to the practice of immunologists due to referrals for consultation or for intravenous immunoglobulin (IVIG) treatment. This review aims to explore the relationship between chronic Lyme disease, post-treatment Lyme disease syndrome, and the immune system. Here, we review the current literature on (1) issues in conventional and alternative diagnostic testing for Lyme disease, (2) the hypothesis that B. burgdorferi infection can persist despite appropriate use of recommended antibiotics, (3) current theories regarding B. burgdorferi's role in causing both immune dysregulation and protracted symptoms, and (4) the use of IVIG for the treatment of Lyme disease.

Cognitive Decline in Post-treatment Lyme Disease Syndrome.

OBJECTIVE: Patient-reported cognitive complaints are common in those with post-treatment Lyme disease syndrome (PTLDS). Objective evidence of cognitive impairment in this population is variable in part due to methodological variability in existing studies. In this study, we sought to use a systematic approach to characterizing PTLDS based on the most current consensus diagnosis. We further examined PTLDS-related cognitive decline, operationalized as a significant decline in cognitive test performance relative to premorbid cognitive ability. METHOD: We enrolled a case series of 124 patients with confirmed PTLDS defined by Infectious Diseases Society of America-proposed case definition. Cognitive functioning was evaluated using standardized neuropsychological measures. RESULTS: The majority (92%) of participants endorsed some level of cognitive difficulty, yet 50% of the sample showed no statistically or clinically significant cognitive decline, 26% of the sample evidenced significant cognitive decline on measures of memory and variably on measures of processing speed, and 24% of the sample were excluded from analyses due to suboptimal test engagement. CONCLUSIONS: The current findings are consistent with the literature showing that the most robust neurocognitive deficit associated with PTLDS is in verbal memory and with variable decline in processing speed. Compared to population normative comparison standards, PTLDS-related cognitive decline remains mild. Thus, further research is needed to better understand factors related to the magnitude of subjective cognitive complaints as well as objective evidence of mild cognitive decline.

Association of small fiber neuropathy and post treatment Lyme disease syndrome.

OBJECTIVES: To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction. METHODS: This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored. RESULTS: 10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv. CONCLUSIONS: SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

Neurocognition in Post-Treatment Lyme Disease and Major Depressive Disorder.

OBJECTIVE: Neurocognitive dysfunction in patients with residual or emergent symptoms after treatment for Lyme Disease is often attributed to comorbid depression. In this study, patients with Post-Treatment Lyme Disease Syndrome (PTLDS) were compared to patients with Major Depressive Disorder (MDD), as well as healthy comparison subjects (HC), on neurocognitive measures administered through the same laboratory, to determine if patterns of performance were similar. METHODS: Two analyses were conducted. First, performance on the Wechsler Adult Intelligence Scale (WAIS-III) and on subtests from the Wechsler Memory Scale (WMS-III) was compared among the groups. Second, comparable subgroups of PTLDS and MDD patients with at least one low WMS-III score were compared on an additional set of measures assessing motor function, psychomotor performance, attention, memory, working memory, and language fluency, to determine if the overall profile of performance was similar in the two subgroups. RESULTS: In the first analysis, PTLDS patients performed more poorly than both MDD and HC on tasks assessing verbal abilities, working memory, and paragraph learning. Processing speed in the two patient groups, however, was equally reduced. In the second analysis, MDD patients with low WMS-III exhibited concomitantly greater difficulties in psychomotor speed and attention, while low-WMS-III PTLDS patients exhibited greater difficulties in language fluency. CONCLUSIONS: MDD and PTLDS can be confused neuropsychologically because both exhibit similar levels of psychomotor slowing. However, problems on memory-related tasks, though mild, are more pronounced in PTLDS. PTLDS patients with poorer memory also exhibit poorer language fluency, and less deficit in processing speed and attention compared to MDD.