Lyme Disease: What the Neuroradiologist Needs to Know.

Lyme disease is the most common tick-borne disease in Canada and the United States, caused by Borrelia burgdorferi, which affects multiple organ systems. Epidemiology, clinical presentation, and neuroimaging findings are reviewed.

An Interesting Presentation of Lyme Pseudothrombophlebitis.

An 8-year-old boy presented to the emergency department with swelling and pain of his left knee and calf for approximately 1 week. His examination was significant for moderate knee effusion and swelling of the posterior calf with erythema and warmth of the affected areas. An ultrasound obtained at an outside hospital showed a large heterogeneous mass in the gastrocnemius, and a magnetic resonance imaging revealed a large, heterogeneous, rim-enhancing collection in the medial head of the left gastrocnemius muscle with surrounding myositis involving the gastrocnemius muscle. The child was taken to the operating room by the orthopedic team for drainage and irrigation of the knee effusion and of the collection in the gastrocnemius. The diagnosis of Lyme pseudothrombophlebitis was made through Lyme serology testing of aspirated fluid. He improved after this drainage but required a prolonged antibiotic course.

Single-photon emission tomography imaging in patients with Lyme disease treated with human embryonic stem cells.

Aim The purpose of this study was to evaluate the longitudinal changes in brain perfusion in patients with Lyme disease treated with human embryonic stem cells. Material and methods The study included 59 (age range 41.68 ± 16.37 years) patients with Lyme disease whose single-photon emission tomography imaging was performed before and after the human embryonic stem cell therapy. Technetium-hexa methyl propylene aminoxime single-photon emission tomography imaging was used to assess the hypoperfused lesions/regions in the brain prior to the therapy, as well as the improvement in perfusion after human embryonic stem cell treatment. Results After receiving human embryonic stem cell therapy, single-photon emission tomography imaging reflects a significant (>60%) improvement in 43 patients along with moderate (30-60%) and mild (<30%) improvement in 12 and four patients, respectively. The cerebral perfusion flow improved and the degree of hypoperfusion in the other regions significantly decreased after the human embryonic stem cell therapy. Interpretation of single-photon emission tomography imaging of brain images (before and after therapy) clearly presented the changes in color at various brain regions which represent the improvements in patients. Conclusion Single-photon emission tomography imaging could be used as a potential diagnostic tool to assess the response of Lyme disease patients to human embryonic stem cell therapy.

In vivo imaging of Lyme arthritis in mice by [18F]fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVE: Lyme borreliosis (LB) is a tick-borne infectious disease caused by Borrelia burgdorferi spirochaetes, which are able to disseminate from the tick-bite site to distant organs. Mouse models are widely used to study LB and especially Lyme arthritis (LA), but only a few whole-animal in vivo imaging studies on the pathogenesis of B. burgdorferi infection in mice have been published so far. The existing imaging techniques have their drawbacks and, therefore, novel tools to complement the array of available LB imaging methodologies are needed. METHOD: The applicability of positron emission tomography combined with computed tomography (PET/CT) imaging was evaluated as a method to monitor LB and especially LA in the C3H/HeN mouse model infected with wild-type B. burgdorferi N40 bacteria. The imaging results were compared with the traditional LA analysis methods, such as tibiotarsal joint swelling and histopathological assessment of joint inflammation. RESULTS: PET/CT imaging provided high-resolution images with quantitative information on the spatial and temporal distribution of the [18F]fluorodeoxyglucose ([18F]FDG) tracer in B. burgdorferi-infected mice. The [18F]FDG accumulated in the affected joints and activated lymph nodes of infected mice, while the tracer signal could not be visualized in these organs in uninfected control animals. Importantly, in vivo PET/CT imaging data were in agreement with the histopathological scoring of inflammation of mouse joints. CONCLUSION: PET/CT imaging with [18F]FDG is a reliable method to longitudinally monitor the development and progression of B. burgdorferi infection-induced inflammation in vivo in mouse joints.

Detection of Bioluminescent Borrelia burgdorferi from In Vitro Cultivation and During Murine Infection.

Borrelia burgdorferi, etiologic agent of Lyme disease, is the leading tick-borne disease in the United States with approximately 300,000 cases diagnosed annually. Disease occurs in stages beginning localized infection at the site of a tick bite and progresses to disseminated infection when antibiotic treatment is not administered in a timely manner. A multi-systemic infection develops following dissemination to numerous immunoprotective tissues, such as the heart, bladder, and joints, resulting in late Lyme disease. B. burgdorferi undergoes dynamic genetic regulation throughout mammalian infection and defining the exact role of virulence genes at distinct stages of disease is challenging. The murine model allows for the characterization of the pathogenic function of genes in B. burgdorferi, but traditional end point studies limit the ability to gather data throughout an infection study and greatly increase the required number of mice. Molecular genetic techniques to evaluate and quantitate B. burgdorferi infection are laborious and costly. To partly circumvent these issues, a codon optimized firefly luciferase, under the control of a constitutive borrelial promoter, was introduced into B. burgdorferi enabling the characterization of mutant or modified strains under in vitro growth conditions and throughout murine infection. The detection of bioluminescent B. burgdorferi is highly sensitive and allows for the repeated real-time quantitative evaluation of borrelial load during murine infection. Furthermore, bioluminescence has also been utilized to evaluate alteration in tissue localization and tissue-specific gene expression of B. burgdorferi. In this chapter, we describe the generation of bioluminescent borrelial strains along with methods for in vitro, in vivo, and ex vivo B. burgdorferi studies.

Targeting of vascular adhesion protein-1 by positron emission tomography visualizes sites of inflammation in Borrelia burgdorferi-infected mice.

BACKGROUND: In the present study, we sought to evaluate the feasibility of targeting vascular adhesion protein-1 (VAP-1) by positron emission tomography (PET) for the longitudinal quantitative assessment of Borrelia burgdorferi infection-induced inflammation in mice. METHODS: Mice with B. burgdorferi infection-induced arthritis were studied. During a 7-week follow-up period, the progression of arthritis was monitored weekly with 68Ga-DOTA-Siglec-9 PET/computed tomography (CT) and measurement of tibiotarsal joint swellings. A subgroup of infected mice was treated with ceftriaxone. Finally, histopathological assessment of joint inflammation was performed and VAP-1 expression in joints were determined. RESULTS: Explicit joint swelling and 68Ga-DOTA-Siglec-9 uptake could be demonstrated in the affected joints from B. burgdorferi-infected mice. By contrast, no obvious accumulation of 68Ga-DOTA-Siglec-9 was detected in joints of uninfected mice. The maximum swelling and highest uptake in the affected joints were observed 4 weeks after the infection. 68Ga-DOTA-Siglec-9 uptake in joints correlated with joint swelling (P < 0.0001) and histopathological scoring of inflammation (P = 0.020). Despite short-term antibiotic treatment, the arthritis persisted, and the PET signal remained as high as in nontreated mice. Immunohistochemistry revealed strong-to-moderate expression of VAP-1 in the synovium of B. burgdorferi-infected mice, while only weak expression of VAP-1 was detected in uninfected mice. CONCLUSIONS: The present study showed that 68Ga-DOTA-Siglec-9 can detect B. burgdorferi infection-induced arthritis in mice. Furthermore, longitudinal PET/CT imaging allowed monitoring of arthritis development over time.

Optic neuritis and chorioretinitis as ocular manifestations of borreliosis in Brazil: three cases reported / Neurite óptica e coriorretinite como manifestações oculares da borreliose no Brasil: três casos relatados

Abstract Lyme disease is a systemic infection caused by a tick bite and transmission of the Borrelia burgdorferi spirochete. Species of tick vectors of the disease infest mainly wild or rural animals and rodents that may be asymptomatic reservoirs of the bacteria. Characteristic of the northern hemisphere, Lyme disease in Brazil takes on different characteristics, complicating diagnosis. This paper aims to describe three cases of Lyme-like disease in a city in the state of Bahia, Brazil, with ophthalmologic findings.

Resumo A doença de Lyme é uma infecção sistêmica causada pela picada do carrapato e transmissão da espiroqueta Borrelia burgdorferi. As espécies de carrapatos vetores da doença infestam, principalmente, animais silvestres, rurais e roedores que podem ser reservatórios assintomáticos da bactéria. Característica do hemisfério norte, a doença de Lyme no Brasil assume características distintas, dificultando seu diagnóstico. Esse trabalho tem por objetivo, descrever três casos da doença Lyme símile do Brasil, com achados oftalmológicos, em município do Estado da Bahia.

Full-thickness macular hole: a rare complication of Borrelia burgdorferi neuroretinitis.

Borrelia burgdorferi is a known infective cause of neuroretinitis. We present a case of B burgdorferi neuroretinitis complicated by macular hole in a 22-year-old man. The neuroretinitis was managed with early high-dose intravenous corticosteroid and oral antibiotic. The macular hole was managed with macular hole surgery after intraocular inflammation had resolved.

Transplantation of Human Embryonic Stem Cells in Patients with Multiple Sclerosis and Lyme Disease.

BACKGROUND Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease in which the myelin sheath of nerve cells is damaged. It can cause delayed neurologic symptoms similar to those seen in Lyme disease (LD) patients. Thymus derived T-cells (myelin reactive) migrate to the blood brain barrier and stimulate an inflammatory cascade in the central nervous system. Cell based therapies play an important role in treating neurological diseases such as MS and LD. CASE REPORT Human embryonic stem cell (hESC) therapy was used to treat two patients with both MS and LD. The hESCs were administered via different routes including intramuscular, intravenous, and supplemental routes (e.g., deep spinal, caudal, intercostal through eye drops) to regenerate the injured cells. Both the patients showed remarkable improvement in their functional skills, overall stamina, cognitive abilities, and muscle strength. Furthermore, the improvement in the patients' conditions were assessed by magnetic resonance tractography and single photon emission computed tomography (SPECT). CONCLUSIONS Therapy with hESCs might emerge as an effective and safe treatment for patients with both MS and LD. Well-designed clinical trials and follow-up studies are needed to prove the long-term efficacy and safety of hESC therapy in the treatment of patients with MS and LD.

5-hydroxytryptamine and Lyme disease. Opportunity for a novel therapy to reduce the cerebellar tremor?

Lyme boreliosis is caused by the spirochete Borrelia burdorferi, which is transmitted by ticks. A 59 year-old woman developed pyrexia, strong headaches, ataxia, dysarthria and tremor of the limbs after a tick bite. She was unable to work and eat on her own. She was hospitalized three times and diagnosed with cerebellar intention tremor, cerebellar ataxia, dysarthria, bilateral horizontal gaze paralysis and a central lesion of the left facial nerve. There were no pyramidal, sensory or psychiatric disturbances. The brain MRI showed multifocal leucoencephalopathy with many hyperintense areas in both hemispheres, as well as in the left superior pedunculus cerebellaris. Diagnosis was confirmed by serologic examination. Treatment with cephtriaxone, doxycycline, methylprednisolone, cephixime and ciprofloxacine was administered without effect on the tremor, ataxia and horizontal gaze paralysis. Treatment was then administered with 5-hydroxytriptamine (5-HT) in increased doses. The result of the three-month treatment with 5-HT was a gradual diminution of the tremor and the ataxia and an increase in the ability to eat, walk and work independently.

Lyme disease-related intracranial hypertension in children: clinical and imaging findings.

Lyme disease (LD) is a tick-borne infection that is endemic to multiple areas of the United States. Patients with LD may present with sign and symptoms of intracranial hypertension (IH). The objective of this study is to evaluate the history, clinical findings, CSF analysis, and brain imaging results in pediatric patients with increased intracranial pressure secondary to LD. A retrospective database search was performed using the International Classification of Diseases (ICD) 9/10 codes to identify patients diagnosed with LD and IH between 2004 and 2014 at a tertiary referral pediatric hospital. Clinical, laboratory and neuroimaging data for each patient were reviewed. Seven patients met inclusion criteria; mean age was 9.6 years (standard deviation 4.0 years); 4/7 patients were male. Average body mass index was 18.8 kg/m(2) (standard deviation 3.0 kg/m(2)). Fever was present in four patients. Four had a history of LD related erythema migrans. All had elevated CSF opening pressure with leukocytosis and lymphocytic predominance. MRI obtained in six patients showed contrast enhancement of various cranial nerves. Tentorial enhancement was noted in all patients. In addition, patients had widening of the optic nerve sheath (ONS), optic nerve protrusion, and flattening of the posterior globe consistent with increased intracranial pressure. All patients had resolution of their symptoms after initiation of antibiotic therapy. In endemic areas, LD should be included in the differential of IH. MRI can help distinguish IH due to LD from its idiopathic form due to the presence of tentorial and cranial nerve enhancement in the former in addition to abnormal CSF showing leukocytosis with lymphocyte predominance.

Cardiac Magnetic Resonance Characterizes Myocarditis in a 16-Year-Old Female With Lyme Disease.

Myocarditis may occur during early disseminated Lyme disease. A 16-year-old girl with serologic evidence of Borrelia burgdorferi infection and transient first-degree atrioventricular block underwent cardiac magnetic resonance imaging, which demonstrated myocardial hyperemia, edema, and delayed gadolinium enhancement. We discuss the use of T1- and T2-weighted dark blood sequences in addition to inversion recovery delayed enhancement imaging to support the diagnosis of Lyme myocarditis.

SPECT brain imaging in chronic Lyme disease.

OBJECTIVES: Lyme disease is an infectious disease that frequently involves the central nervous system, leading to cognitive and/or mood dysfunction. The basis for these symptoms remains to be defined but may be the result of a vasculitis or metabolic abnormality secondary to the infection. SPECT scans of the brain might provide an objective measure of abnormalities present in patients with otherwise difficult to objectify clinical findings. The objective of this study was to determine the frequency, location, and severity of abnormalities in SPECT scans of the brain of patients with chronic Lyme disease. METHODS: A total of 183 individuals who met the clinical definition of chronic Lyme disease underwent SPECT scanning of the brain using Tc and standard nuclear imagine techniques. Abnormalities of perfusion to affected areas of the brain were defined as mild, moderate, or severe. RESULTS: Of all patients, 75% demonstrated abnormalities in perfusion to various areas of the brain, most notably the frontal, temporal, and parietal lobes. Patients considered to be seropositive and those considered seronegative had similar rates, types, and severity of perfusion defects. Abnormalities of MRI of the brain were seen in 14% of patients. Treatment with antibiotics, especially those with intracellular-penetrating activity, resulted in resolution or improvement of abnormalities in 70% of patients over a 1- to 2-year period. CONCLUSIONS: Brain SPECT scans are abnormal in most patients with chronic Lyme disease, and these scans can be used to provide objective evidence in support of the clinical diagnosis. The use of certain antibiotic regimens seems to provide improvement in both clinical status and SPECT scans.

Ultrasonographic evaluation of knee joints in patients with Lyme disease.

OBJECTIVE: The aim of this study was to evaluate the ultrasonographic images of patients with chronic knee pain and serologic features of Lyme disease. METHODS: Seventy-six patients hospitalized in The Department of Infectious Diseases and Neuroinfections of the Medical University in Bialystok, Poland were included in the study. Patients were divided into two groups: (1) the Lyme disease group included patients with pain in one or both knees and anti-Borrelia burgdorferi antibodies with symptoms lasting for over 6 months; (2) the control group included patients suffering from pain in one or both knees for over 6 months, but for whom B. burgdorferi infection was excluded. RESULTS: The most frequent ultrasonographic finding in the Lyme disease group was effusion, and its frequency was significantly higher than in the control group. No patient in the control group presented with synovitis or cartilage damage, while these were quite frequent findings in the Lyme disease group. Baker's cysts were more frequent in the Lyme disease group, but this was statistically non-significant. CONCLUSIONS: Ultrasonography may be useful in following the sequelae of Lyme disease. The abnormalities found in Lyme disease patients are non-specific and ultrasonography is not useful in the differential diagnosis.

Avellis syndrome due to borreliosis.

Avellis syndrome is a rare form of alternating hemiparesis that is usually because of atherosclerosis. We report a 67-year-old man who developed paresthesiae of the left arm, dysphagia and dysphonia. The clinical picture, magnetic resonance imaging and cerebrospinal fluid findings were consistent with Avellis syndrome caused by brain stem arteritis because of late stage Borrelia burgdorferi infection, an extremely unusual aetiology for Avellis syndrome; this may well be the first such instance. It may be unrecognized in elderly patients with other risk factors for cerebrovascular disease.