Lyme neuroborreliosis (LN) is one of the many forms of Borrelia spp. infection, a spirochetal bacterial pathogen that is transmitted to the human host after a tick bite, specifically from Ixodes species [1] [2] [3] [4]. Higher prevalence is encountered in the United States (where Borrelia burgdorferi is the main causative agent, with an incidence rate of 9.1 cases per 100 000 individuals), and in Europe, where B. garinii, B. afzelii and B. burgdorferi sensu stricto are identified as main pathogenic species [2] [4]. In order for LN to occur, patients first pass through the initial stages of borreliosis (commonly known as Lyme disease) - the appearance of erythema migrans (a sharply-defined circular or "target" lesion that develops in the proximity of the tick bite) within a period of 3-30 days after the bite, and constitutional complaints such as fever, headaches, joint pain, and fever [1] [3] [4]. LN appears when bacteria are disseminated into the peripheral and central nervous system (CNS) and findings are seen either during early stages of dissemination or after a delayed period of weeks to years as a late manifestation [3] [4]. LN is frequently described as a complication of Lyme disease in Europe than in the United States (35% vs. <10%, respectively) [3]. Headaches, cranial nerve palsies (mainly of the facial nerve, presenting as either unilateral or bilateral face droop), and papilledema are nonspecific features, which may prolong the time before a correct diagnosis is made, particularly in children where enteroviral meningitis is a common cause of such symptoms [3] [5]. A more prolonged clinical course and CNS abnormalities, however, are useful distinguishing characteristics [5]. The term Bannwarth's syndrome is used to describe the typical signs of LN (mainly seen in European patients) - lymphocytic meningitis, radiculitis accompanied by sharp pain lasting for weeks or months (with exacerbations during the night), and cranial neuritis [1] [3] [4] [6]. Apart from the involvement of the peripheral nervous system, Borrelia spp. can reach the CNS and cause significant damage to the brain and the spinal cord, presenting as a variable change in consciousness (from mild confusion to severe and life-threatening encephalitis) [1].

• Pain

  Cranial paresis and other neurologic signs usually occur after the onset of pain. The present paper describes four patients who had severe pain as the main presenting symptom of Lyme neuroborreliosis. [ncbi.nlm.nih.gov]

  Chronic and diffuse pain and fatigue disorders with non-specific neurological symptoms are common in the general population. [tidsskriftet.no]

• Fever

  Elevated lactate levels were accompanied by fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. [ncbi.nlm.nih.gov]

  Some synonyms in other countries include "tick typhus", "tobia fever" in Columbia, "São Paulo fever" or "febre maculosa" in Brazil and "fiebre manchada" in Mexico. [web.archive.org]

  Neither is the disease related to Rocky Mountain spotted fever, a common tick-borne disease in Montana that causes fever and fatigue and if left untreated a rash called black measles and in some cases death. ''We know what it isn't,'' said Dr. [nytimes.com]

  headaches, joint pain, and fever. [symptoma.com]

• Fatigue

  Patients and healthy controls were assessed for quality of life [Short Form (36) with subscores for physical and mental components (PCS, MCS)], fatigue (fatigue severity scale), depression (Beck depression inventory), verbal memory and learning and cognitive [ncbi.nlm.nih.gov]

  Conclusions: LNB can present as acute ocular motor disorders in conjunction with fatigue and other clinical manifestations. [mayoclinic.pure.elsevier.com]

  Chronic fatigue states have been reported to occur following any number of infections, including Lyme disease. [doi.org]

• Weakness

  Clinical examination revealed motor radiculopathy with bilateral areflexia of biceps reflex and asymmetric muscle weakness of shoulder elevation and flexion of the forearms. [thieme-connect.com]

  A 15-year-old boy had onset of unilateral facial weakness. A few days later, he experienced mild vertigo, double vision, and headache. Examination confirmed a peripheral right seventh nerve weakness in addition to an internuclear ophthalmoplegia. [ncbi.nlm.nih.gov]

• Chills

  The rash is often accompanied by flulike symptoms, such as headache, fatigue, chills, loss of appetite, fever, and aching joints or muscles. [britannica.com]

  Early localized stage (3-30 days post-tick bite) Red, expanding rash called erythema migrans (EM) Fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes Some people may get these general symptoms in addition to an EM rash, but [web.archive.org]

• Dyspnea

  The patient presented with dyspnea and pain behind the sternum, which had been occurring for several months, mainly during fast walking upstairs. The patient reported having no symptoms when he was motionless. [doi.org]

  […] within one to two months after infection (range of less than one week to seven months). 17 – 19 Lyme carditis is a less common complication of systemic disease, occurring in approximately 4 to 10 percent of patients. 19 It may present as chest pain, dyspnea [web.archive.org]

  Hospitalization and continuous monitoring, with consideration for temporary pacing, are advisable for patients with any of the following: Associated symptoms (eg, syncope, dyspnea, or chest pain) Second-degree or third-degree AV block First-degree heart [emedicine.medscape.com]

• Nausea

  Five of the patients presented with severe fatigue, malaise, nausea, headache and fever. Four had recognised a tick bite recently, and two developed erythema migrans. [mayoclinic.pure.elsevier.com]

  Nausea and vomiting are rare. A solitary lesion is the most frequent presentation in both US (81%; 95% confidence interval [CI], 72%-87%) and European patients (88%; 95% CI, 81%-93%). [doi.org]

• Gagging

  A 26-kDa Borrelia glycosaminoglycan-binding (GAG-binding) protein, Bgp, binds to the GAG side chains of heparan sulfate on endothelial cells, and to both heparan sulfate and dermatan sulfate on neuronal cells ( 49, 50 ). [doi.org]

• Palpitations

  Palpitations, bradycardia, bundle branch block, or myocarditis alone are not criteria for cardiovascular involvement. [web.archive.org]

  Symptoms of early disseminated Lyme disease (stage 2) may occur weeks to months after the tick bite, and may include: Numbness or pain in the nerve area Paralysis or weakness in the muscles of the face Heart problems, such as skipped heartbeats (palpitations [nlm.nih.gov]

• Skin Lesion

  EM skin lesion) and from CSF; and (4) more frequently fulfilled microbiologic criteria for established borrelial infection of the central nervous system. [ncbi.nlm.nih.gov]

  Table 3 Comparison of the characteristics of erythema migrans (EM)—like skin lesions. Table 3 Comparison of the characteristics of erythema migrans (EM)—like skin lesions. [doi.org]

• Eruptions

  Associated with this eruption are inflammation and enlargement of the adjacent lymphatics and lymph nodes, fever, headache, and a rash radiating from the wound site and lasting about 48 hours. [ncbi.nlm.nih.gov]

  […] potency should be considered when tetracyclines are prescribed during summertime: a study on doxycycline and lymecycline in human volunteers, using an objective method for recording erythema, Br J Dermatol, 1994, vol. 130 (pg. 356 - 60 ) 33 Phototoxic eruptions [doi.org]

• Back Pain

  Back pain is a common symptom among patients presenting to the acute medical unit. We describe the case of a 55-year-old man with a brief history of fatigue and severe back pain, unresponsive to escalating doses of opiate analgesia. [ncbi.nlm.nih.gov]

   Flu-like illness  Headache  Extreme Fatigue  TMJ/ Jaw Pain (Temporomandibular Join)  Neck & Back Pain  Joint Pain & Swelling, Bone Pain (EM) Rash 6. [slideshare.net]

  Next day I was in agony with horrendous back pain. For the next two weeks I barely slept. Lying down was impossible. I got no relief from painkillers. A 24 hour bout of foul diarrhoea was distressing, and I felt ill. [bmj.com]

  She suffered from back pain radiating to chest, arms, head and neck, especially intense at night time, and after 2 weeks she also developed bilateral facial palsy. [insightsimaging.springeropen.com]

  paresthesias, nausea, vomiting, malaise, fatigue, neck pain, lower back pain, arthralgia, myalgia)—and to score the intensity of each present symptom from 1 to 10. [cid.oxfordjournals.org]

• Diplopia

  A 22-year-old male presented with history of flu-like illness and headache, accompanied by vertical binocular diplopia, worse on downgaze and better in upgaze and right head tilt. [ncbi.nlm.nih.gov]

  Other symptoms may include diplopia, hearing impairment, paralysis, altered sensation, difficulty in walking or cognitive impairment. [tidsskriftet.no]

  She had experienced continuing headaches, lethargy and a self-limiting episode of diplopia that prompted her to see her general practitioner. [mja.com.au]

  A 71-year-old woman with headache, malaise, fever, and diplopia. Initial coronal postcontrast T1 MR imaging ( A and B ) with enhancing bilateral third and fifth cranial nerves. [doi.org]

  A 71-year-old woman with headache, malaise, fever, and diplopia. Initial coronal postcontrast T1 MR imaging (A and B) with enhancing bilateral third and fifth cranial nerves. [ajnr.org]

• Photophobia

  Clinical record A 58-year-old woman of European ancestry presented to a rural hospital in New South Wales in May 2014 with an 8-month history of worsening motor instability, confusion and bilateral occipital headaches associated with photophobia, lethargy [mja.com.au]

  Photophobia As in various other infections and/or CNS disturbances (e.g. meningitis, migraine, psittacosis, typhus, Rocky Mountain Spotted Fever), photophobia may be a prominent feature. In our sample, 70% of respondents reported photophobia. [lymenet.org]

• Prolapse

  […] presentations include paralysis of the diaphragm or abdominal muscles.2 Rarely, patients may present with Guillain-Barre syndrome and CSF pleocytosis.5 The differential diagnosis includes diseases with neuropathy and/or CSF pleocytosis such as disc prolapse [pmj.bmj.com]

• Headache

  We present two patients with monosymptomatic headache resembling chronic tension-type headache as the first manifestation of Lyme neuroborreliosis. [ncbi.nlm.nih.gov]

  The ailment is primarily seen during the summer months and symptoms range from headaches and facial nerve palsy to severe sensory and motor deficits with altered consciousness. [symptoma.com]

  Five of the patients presented with severe fatigue, malaise, nausea, headache and fever. Four had recognised a tick bite recently, and two developed erythema migrans. [mayoclinic.pure.elsevier.com]

• Encephalopathy

  Lyme Disease — Encephalopathies, Lyme Disease — Lyme Disease Encephalopathies — Lyme Disease Encephalopathy — Lyme Disease Mononeuritis Multiplex — Mononeuritis Multiplex, Lyme Disease — Peripheral Nervous System Lyme Disease — Lyme Meningoradiculitis [mesh.kib.ki.se]

  The well-documented neurologic spectrum includes lymphocytic meningitis, cranial neuropathy, and radiculoneuritis in the early disseminated stage; and peripheral neuropathy, chronic encephalomyelitis, and mild encephalopathy in the late persistent stage [ncbi.nlm.nih.gov]

• Radiculitis

  Neurogenic pain with radiculitis is often the starting symptom in adult patients with tick-borne Lyme neuroborreliosis and in some cases the only clinical manifestation. [ncbi.nlm.nih.gov]

  Most patients experience subacute onset of neurological symptoms weeks or months after infection, the most common being facial nerve palsy or focal neurogenic pain owing to radiculitis ( 1, 2 ). [tidsskriftet.no]

• Radiculopathy

  Prognosis in neuroborreliosis related motor radiculopathy is excellent in the majority of cases, and antimicrobial treatment the only necessary therapy. [thieme-connect.com]

  We reviewed thirty cases of acute Lyme disease in the West of Ireland and found neurological syndromes in 15 (50%), with painful radiculopathy (12 patients; 80%) and cranial neuropathy (7 patients; 46%) occurring frequently. [ncbi.nlm.nih.gov]

  BWS is characterized by painful radiculopathy, neuropathy, varying degrees of motor weakness and facial nerve palsy, and cerebrospinal fluid (CSF) lymphocytic pleocytosis.Over 3 weeks between July and August 2017, Mayo Clinic campuses in Minnesota and [canlyme.com]

  Theel Published 2018 in Open forum infectious diseases DOI: 10.1093/ofid/ofx276 Bannwarth syndrome (BWS), an infrequent manifestation of neuroinvasive Lyme disease (LD) characterized by radiculopathy, neuropathy, and lymphocytic pleocytosis, is more commonly [semanticscholar.org]

• Cranial Neuropathy

  Presenting neurological syndromes include meningitis, cranial neuropathies, myeloradiculitis and mononeuritis multiplex. A lack of specificity in serological diagnosis may add to diagnostic confusion. [ncbi.nlm.nih.gov]

The diagnosis of LN is a difficult one to make without a proper clinical and microbiological investigation. The physician should first conduct a detailed patient interview during which the incidence of tick bites and typical skin lesions must be assessed, whereas a comprehensive travel history (given the fact that visiting endemic areas is a risk factor) may provide important clues as well [1] [4]. Tick-borne disease must be considered in all patients with undisclosed cutaneous and constitutional symptoms in the summer months, as the vast majority of such events occur from May to September [1] [2]. After a detailed physical examination (particularly focused on neurological evaluation), laboratory studies are the cornerstone for confirming the condition. Current recommendations advocate initial serological testing (through enzyme immunoassays or enzyme-linked immunosorbent assays - EIA and ELISA, respectively) of cerebrospinal fluid (CSF) or blood for immunoglobulin (Ig) G and IgM antibodies, followed by more sensitive methods such as Western blot [1] [4] [6] [7] [8]. CSF examination yields lymphocytic pleocytosis with normal biochemical composition [4], and the detection of neutrophilic predominance can firmly exclude Lyme disease as the etiology of neurologic infections [5]. Polymerase chain reaction (PCR) testing is a novel technique that allows identification of pathogenic DNA and its implementation is recommended whenever possible [4] [7]. Imaging studies of the endocranium and the CNS, magnetic resonance imaging (MRI) being the main candidate, reveal nonspecific findings and thus are of limited benefit for discriminating between etiologies of such symptoms [1] [9].

• Cerebrospinal Fluid Abnormality

  The most common form of CNS involvement was a subtle, chronic encephalopathy characterized by memory impairment, often accompanied by cerebrospinal fluid abnormalities [ 17–21 ]. [doi.org]

The CSF mononuclear cell count was used as a surrogate marker of treatment outcome. [ncbi.nlm.nih.gov]

This term arose due to a number of patients reporting persistent non-specific health problems after completing treatment ( 6, 9 ), but the incidence of post-treatment Lyme disease is controversial and its mechanisms unknown ( 7 ). [tidsskriftet.no]

Epidemiologic data, tick bite histories, duration of symptoms, clinical findings, radiologic findings, treatment durations and prognosis were investigated. RESULTS: Totally 7 patients had been treated with the diagnosis of Lyme neuroborreliosis. [ncbi.nlm.nih.gov]

Prognosis is excellent and the time to recovery may be influenced when treated appropriately. [thieme-connect.com]

The book also features a chapter on prognosis, offering an evidence-based review of outcome studies, as well as practical advice to physicians to help them manage the challenging clinical scenario of chronic symptoms attributed to Borrelia infection. [books.google.com]

CSF examination yields lymphocytic pleocytosis with normal biochemical composition, and the detection of neutrophilic predominance can firmly exclude Lyme disease as the etiology of neurologic infections. [symptoma.com]

Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, was isolated from the CSF of a patient with elevated serum IgG antibody titers against B burgdorferi and a history of multiple tick bites. [ncbi.nlm.nih.gov]

It is suggested that the newly discovered spirochete is involved in the etiology of Lyme disease. [doi.org]

The facts about Lyme disease, from epidemiology to treatment to control Lyme borreliosis, popularly known as Lyme disease, remains the most commonly reported tick-transmitted infection in North America and Europe. [books.google.com]

This review highlights differences in the epidemiology, clinical manifestations, diagnosis, and management of Lyme disease in the United States, Europe, and Asia, with an emphasis on neurologic manifestations and neuroimaging. [ncbi.nlm.nih.gov]

Cases such as these can help explain the pathophysiology of mental illness. Research in LAD provokes an avalanche of additional questions. [ncbi.nlm.nih.gov]

A similar pathophysiology occurs in LAD. Method: A retrospective chart review and epidemiological calculations were performed. [doi.org]

Centers for Disease Control and Prevention. Frequently Asked Questions – Lyme Disease. Available online at http://www.cdc.gov/lyme/faq/index.html#accurate. Accessed July 2012. Centers for Disease Control and Prevention. Transmission – Lyme Disease. [labtestsonline.org]

What other steps should I take to prevent bug bites? Prevent mosquito bites Prevent mosquito bites. Cover exposed skin by wearing long-sleeved shirts, long pants, and hats. Stay and sleep in screened or air-conditioned rooms. [web.archive.org]

Here are tips for other preventive actions you can take against ticks. Also see Tips to Prevent Mosquito Bites. Avoid Tick Habitats Reduce time spent in potentially tick-infested habitats such as tall grass and shrubs. [epa.gov]

The best way to prevent Lyme disease is to prevent tick bites: Use protective clothing—wear long-sleeved shirts and pants. Use insect repellents containing DEET or permethrin. [doi.org]

Prompt diagnosis and treatment appear to facilitate symptomatic relief and prevent persistent neurologic deficits. [ncbi.nlm.nih.gov]

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9. Morgen K, Martin R, Stone RD, et al. FLAIR and magnetization transfer imaging of patients with post-treatment Lyme disease syndrome. Neurology. 2001;57:1980–1985.