Lyme neuroborreliosis is a rare zoonosis which can be difficult to diagnose, in particular in low endemic areas. We here report the case of a 35-year-old man presenting with disabling back pain preceded by facial monoplegia, which was wrongly treated as Bell\'s palsy (paralysis a frigore) and then as post-traumatic lumbosciatica. The onset of facial diplegia allowed for a definitive diagnosis. The patient was treated with ceftriaxone and symptoms gradually improved.

Lyme disease is a multisystem infectious disease. It is caused by the dissemination of Borrelia spirochetes after a tick bite. It has various manifestations across different age groups. Commonly involved organs are the skin, joints, and nervous system. Nervous system Lyme disease has a wide spectrum of manifestations. While facial nerve palsy and subacute meningitis are commonly observed in the pediatric population, our case report reveals an uncommon manifestation of the nervous system Lyme disease. A four-year-old patient exhibited mood changes, behavioral issues, and generalized tonic-clonic seizures. Extensive diagnostic workup initially yielded no clear cause until positive IgM and IgG serology for Borrelia suggested Lyme neuroborreliosis. This differs from the usual symptoms seen in pediatric cases. The patient responded positively to antibiotic treatment, but persistent post-treatment behavioral issues raised questions about potential long-term effects. This case underscores the importance of considering Lyme disease in atypical presentations, even in non-endemic areas, necessitating an adaptable diagnostic approach for improved outcomes, especially in pediatric patients. Continued research into the comprehensive understanding of Lyme disease in pediatric patients is crucial.

Affections of the central nervous system (CNS) rarely occur in Lyme neuroborreliosis (LNB). CNS manifestations can have residual neurological symptoms despite antibiotic treatment. We explored the spectrum of CNS affections in patients with LNB in a tertiary care center in a region endemic for Lyme borreliosis. We retrospectively included patients treated at a tertiary care center from January 2020-December 2021 fulfilling the case criteria for LNB as stated in the current German guideline on LNB. Clinical data, cerebrospinal fluid (CSF) findings and MRI imaging were collected. We included 35 patients with LNB, 24 with early manifestations and 11 with CNS-LNB. CNS-LNB patients had encephalomyelitis (n = 6) or cerebral vasculitis (n = 5). Patients with early LNB and CNS-LNB differed regarding albumin CSF/serum quotient and total protein in CSF. Duration from onset of symptoms until diagnosis was statistically significantly longer in patients with encephalomyelitis. MRI findings were heterogeneous and showed longitudinal extensive myelitis, perimedullar leptomeningeal enhancement, pontomesencephalic lesions or cerebral vasculitis. CNS-LNB can present with a variety of clinical syndromes and MRI changes. No clear pattern of MRI findings in CNS-LNB could be identified. The role of MRI consists in ruling out other causes of neurological symptoms.

Infection with Borrelia burgdorferi spirochetes can cause Lyme neuroborreliosis (LNB). Neuroborreliosis presenting as encephalitis is a rare manifestation. We present a 72-year-old male patient hospitalized after three days of confusion and altered mental status. Initial computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain were both unremarkable. Lumbar puncture showed an elevated number of white blood cells, elevated protein, and normal glucose levels in the cerebrospinal fluid (CSF), normal electroencephalogram (EEG), and negative tests for common microorganisms in the CSF. The patient received treatment with acyclovir and ceftriaxone. Lumbar puncture repeated on day 16 showed a decreasing number of white blood cells. A repeated MRI showed white matter edema, interpreted as encephalitis, while a repeated EEG showed signs of a non-specific cerebral lesion. The first lumbar puncture revealed intrathecal immunoglobulin M (IgM) antibodies against Borrelia and was positive for Borrelia DNA using real-time PCR, and the following lumbar puncture showed both IgM and IgG intrathecal antibody production. These results thus confirmed the diagnosis of Lyme Borrelia encephalitis. The patient improved clinically and was discharged after treatment with ceftriaxone for three weeks. Encephalitis due to LNB should be considered as a differential diagnosis in cases with unexplained neurological symptoms. Changes in MRI and/or EEG might occur late in the course of the disease, underlining the need for repeated tests in unresolved cases.

In previous studies, we showed that fibroblast growth factor receptors (FGFRs) contribute to inflammatory mediator output from primary rhesus microglia in response to live Borrelia burgdorferi. We also demonstrated that non-viable B. burgdorferi can be as pathogenic as live bacteria, if not more so, in both CNS and PNS tissues. In this study we assessed the effect of live and non-viable B. burgdorferi in inducing FGFR expression from rhesus frontal cortex (FC) and dorsal root ganglion (DRG) tissue explants as well as their neuronal/astrocyte localization. Specific FGFR inhibitors were also tested for their ability to attenuate inflammatory output and apoptosis in response to either live or non-viable organisms. Results show that in the FC, FGFR2 was the most abundantly expressed receptor followed by FGFR3 and FGFR1. Non-viable B. burgdorferi significantly upregulated FGFR3 more often than live bacteria, while the latter had a similar effect on FGFR1, although both treatments did affect the expressions of both receptors. FGFR2 was the least modulated in the FC tissues by the two treatments. FGFR1 expression was more prevalent in astrocytes while FGFR2 and FGFR3 showed higher expression in neurons. In the DRG, all three receptor expressions were also seen, but could not be distinguished from medium controls by immunofluorescence. Inhibition of FGFR1 by PD166866 downregulated both inflammation and apoptosis in both FC and DRG in response to either treatment in all the tissues tested. Inhibition of FGFR1-3 by AZD4547 similarly downregulated both inflammation and apoptosis in both FC and DRG in response to live bacteria, while with sonicated remnants, this effect was seen in one of the two FC tissues and 2 of 3 DRG tissues tested. CCL2 and IL-6 were the most downregulated mediators in the FC, while in the DRG it was CXCL8 and IL-6 in response to FGFR inhibition. Downregulation of at least two of these three mediators was observed to downregulate apoptosis levels in general. We show here that FGFR inhibition can be an effective anti-inflammatory treatment in antibiotic refractive neurological Lyme. Alternatively, two biologics may be needed to effectively curb neuroinflammation and pathology in the CNS and PNS.

OBJECTIVE: Residual symptoms after treatment of Lyme disease, sometimes called post-treatment Lyme disease symptoms (PTLDs), are a matter of ongoing controversy. To guide treatment recommendations, a systematic review was performed of the available literature on specific treatment for PTLDs.
METHODS: A systematic literature search of MEDLINE and CENTRAL was performed. No restrictions on case definitions, study types or specific interventions were applied to enable a comprehensive overview of the available literature. Risk of bias was assessed using the Cochrane risk of bias tools for randomized controlled trials. Certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Outcomes of interest were quality of life, fatigue, depression and cognition as well as adverse events.
RESULTS: After screening 1274 records, eight eligible randomized controlled trials were included. Heterogeneity was observed regarding inclusion criteria, intervention, length of treatment and outcome measures. For efficacy outcomes, results are presented narratively due to heterogeneity. Eligible studies show no statistically significant difference between antibiotics and placebo regarding quality of life, cognition and depression. Results for fatigue were inconsistent whilst studies with low risk of bias showed no statistically significant difference between antibiotics and placebo. Meta-analysis of safety outcomes showed statistically significantly more adverse events for antibiotics compared to placebo.
CONCLUSIONS: Available literature on treatment of PTLDs is heterogeneous, but overall shows evidence of no effect of antibiotics regarding quality of life, depression, cognition and fatigue whilst showing more adverse events. Patients with suspected PTLDs should not be treated with antibiotics.

OBJECTIVE: An 80-year-old male patient had complained of proximal paresis of the left leg, pain and sensory disturbances in the left abdomen, exanthema in the left lower abdomen, coprostasis, and severe abdominal pain, as well as a progressive deterioration of his general condition for weeks. The patient had already presented to three other medical centers. Colonoscopy and computed tomography of the abdomen could not explain the pronounced symptomatology. In addition, there was acute elevator paresis of the left leg and severe pruritic rash on both sides of the trunk.
METHODS: At the Israelitisches Krankenhaus Hamburg (IKH), laboratory parameters of urine, stool, and blood, ultrasound, electrocardiogram, and transthoracic echocardiography diagnosis showed no abnormalities. Esophago-gastro-duodenoscopy revealed patchy erythema and moderately severe chronic low-activity Helicobacter-positive gastritis. Colonoscopically, two polyps were ablated. A neurological examination with magnetic resonance imaging and electroneurography also showed normal findings. Evidence of autoimmune or rheumatoid disease was also absent. Finally, analysis of the cerebrospinal fluid revealed a lympho-granulocytic cell count (32/3 lymphocytes, 21/3 granulocytes) and an elevated Borrelia-specific IgG index (Ai) of 20.82. This finding was confirmed by a complementary serological diagnosis, in which Borrelia-specific IgM and IgG antibodies were detected. In sum, Bannwart\'s syndrome was assumed to be the cause of the neurological symptoms. The 21-day borreliosis therapy included doxycycline administration and analgesia with novaminsulfone and pregabalin as needed.
CONCLUSIONS: A complex symptomatology of leg paresis, lower abdominal pain and sensory disturbances, exanthema, and coprostasis in combination with a long-lasting poor general condition were found to be the consequences of atypical neuroborreliosis.

OBJECTIVE: Serum neurofilament light chain (sNfL), an indicator of neuronal damage, is increasingly recognized as a potential biomarker for disease activity in neurodegenerative disorders. In this study, we wanted to investigate sNfL as a prognostic marker in a large, well-defined population of 90 patients with Lyme neuroborreliosis (LNB). In addition, we sought to explore associations between symptoms and sNfL levels during the acute phase of LNB.
METHODS: Patients diagnosed with definite or possible LNB were recruited from a double-blinded, placebo-controlled, multi-center trial, in which the participants were randomly assigned to 2 or 6 weeks of oral doxycycline treatment. The sNfL levels were measured using a single molecule array assay at both diagnosis and 6-month follow-up, and analysed against clinical parameters, variations in symptom burden and long-term complaints as assessed by a composite clinical score.
RESULTS: At the time of diagnosis, approximately 60% of the patients had elevated sNfL levels adjusted for age. Notably, mean sNfL levels were significantly higher at diagnosis (52 pg/ml) compared to 6 months after treatment (12 pg/ml, p < 0.001), when sNfL levels had normalized in the majority of patients. Patients with objective signs of spinal radiculitis had significantly higher baseline sNfL levels compared to patients without spinal radiculitis (p = 0.033).
CONCLUSIONS: Our findings suggest that sNfL can serve as a biomarker for peripheral nerve tissue involvement in the acute phase of LNB. As found in an earlier study, we confirm normalization of sNfL levels in blood after treatment. We found no prognostic value of acute-phase sNfL levels on patient outcome.

In prior studies, the skin lesion erythema migrans (EM) was present for a longer time period before diagnosis of concomitant borrelial meningoradiculoneuritis (Bannwarth\'s syndrome) compared to EM patients without neurologic symptoms. To determine if this observation pertains to other manifestations of Lyme neuroborreliosis (LNB), we compared EM characteristics in patients with borrelial meningoradiculoneuritis (n = 122) to those with aseptic meningitis without radicular pain (n = 72 patients), and to patients with EM but without neurologic involvement (n = 12,384). We also assessed factors that might impact duration. We found that the duration of EM at diagnosis in patients with borrelial meningoradiculoneuritis was not significantly different compared with those with LNB without radicular pain (34 vs. 26 days; p = 0.227). The duration of EM for each of these clinical presentations of LNB, however, was significantly longer than in patients with EM without LNB (10 days; p < 0.001). Contributing factors to this difference might have been that patients with LNB failed to recognize that they had EM or were unaware of the importance of not delaying antibiotic treatment for EM. In conclusion, the duration of the EM skin lesion in EM patients with LNB is longer than in patients with just EM, irrespective of the type of LNB.

Lyme neuroborreliosis (LNB) is a rare infectious disease, caused by Borrelia burgdorferi spirochetes and responsible for a variety of neurological manifestations. The most common manifestations of LNB in children are cranial nerve involvement, especially facial nerve palsy often accompanied by lymphocytic meningitis. In this article, we present a case of a 4-year-old boy presented to our emergency department with abdominal pain evolving for a week and symmetrical ascending progression of weakness responsible for severe respiratory failure. Diagnosis of Guillain-Barré syndrome (GBS) was initially suspected. Although our patient had received 2 courses (each of 5 days) of Intravenous immunoglobulin (IVG) treatment, no clinical improvement was observed. The diagnosis of LNB was confirmed by detection of both IgG and IgM specific antibodies in serum. The patient\'s muscle weakness got better after a 2- week course of Ceftriaxone but respiratory muscle failure didn\'t improve with two extubation failures. Consequently, we decided to conduct plasmapheresis procedures. We managed to extubate the child and discharge him after a good recovery of his symptoms. Pediatricians must consider LNB disease in the differential diagnosis of GBS, especially when the patient didn\'t recover after IVG treatment. This case shows that plasmapheresis could be effective for pediatric neuroborreliosis cases with severe neurological disorders.