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Lyme Neuroborreliosis

Lyme neuroborreliosis is a late manifestation of an infection by Borrelia spp., a tick-borne bacterial pathogen that is known for causing Lyme disease and a range of clinical syndromes. 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. The diagnosis mandates a thorough clinical investigation, followed by microbiological studies.


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].

  • 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]
  • 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]
  • , headaches, joint pain, and fever.[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]
  • 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]
  • The average Fatigue Severity Scale (FSS) score was 4.29. [8] Krupp defined severe fatigue 4.0 in her NIH sponsored clinical trial. [8] The 17 LBN subjects with residual symptoms also presented with a poor quality of life.[danielcameronmd.com]
  • “Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls,” the investigators found.[reuters.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]
  • 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]
  • 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]
  • 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]
  • 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.[ncbi.nlm.nih.gov]
  • 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]
  • Most of the predictive information was provided by the symptoms at 14 days: these included nausea, vomiting, memory and concentration disturbances, malaise, fatigue, headache, and arthralgia ( Supplementary Figure 2 ).[academic.oup.com]
  • 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]
Failure to Thrive
  • An 11 year old boy presented with long standing symptoms of severe weight loss and chronic headache, while the other patient had pre-existing mental and motor retardation and developed seizures and failure to thrive.[ncbi.nlm.nih.gov]
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]
  • In comparison to patients with normal CSF cell counts, those with pleocytosis more often reported radicular pain, sleep disturbances, and lower back pain, and more often had meningeal signs and peripheral facial palsy (Table 1, Figure 2 ).[cid.oxfordjournals.org]
  • Meningoradiculitis due to borreliosis presenting as low back pain only. Neuroradiology 1998 ; 40 : 126 –27 Ljostad U, Okstad S, Topstad T, et al. Acute peripheral facial palsy in adults. J Neurol 2005 ; 252 : 672 –76 Lesser RL.[doi.org]
  • 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]
  • Two children presented with acquired nystagmus, one with combined nystagmus and partial sixth nerve palsy, one with partial sixth nerve palsy, one with ptosis and one with Adie's pupil.[ncbi.nlm.nih.gov]
  • Results: Two children presented with acquired nystagmus, one with combined nystagmus and partial sixth nerve palsy, one with partial sixth nerve palsy, one with ptosis and one with Adie's pupil.[mayoclinic.pure.elsevier.com]
  • Cranial nerve disorders: facial palsy (sometimes involving both sides of the face), double vision, drooping eyelid (ptosis), numbness pain and tingling of the face, hearing loss, dizziness and tinnitus. Seizures.[lymediseaseaction.org.uk]
  • 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]
Auditory Hallucination
  • He presented with metamorphopsia and auditory hallucinations in the absence of previous tick bites or other signs of Lyme disease.[ncbi.nlm.nih.gov]
Urinary Incontinence
  • A 74-year-old woman presented with gait impairment, urinary incontinence, and dementia. She showed lymphocytic CSF pleocytosis and pronounced intrathecal Borrelia burgdorferi antibody production, indicating active Lyme neuroborreliosis.[ncbi.nlm.nih.gov]
  • 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]
  • , 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]
  • 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]
  • Paresthesia, pain and persistent facial palsy was also significantly more common in patients treated because of neuroborreliosis. Our study shows that persisting neurological symptoms are common after a neuroborreliosis infection.[ncbi.nlm.nih.gov]
  • Residual neurological symptoms, such as facial palsy, concentration disorder, paresthesia and/or neuropathy, were reported by 28/114 patients.[doi.org]
Neck Stiffness
  • In a multivariate analysis, both gender and having headache and neck stiffness were associated with a higher level of pleocytosis.[ncbi.nlm.nih.gov]
  • stiffness during their acute illness (87% compared with 13%; odds ratio, 2.4 [CI, 1.0 to 5.5]; P 0.045); however, the performance of the two groups on neurocognitive tests did not significantly differ.[doi.org]
  • stiffness due to meningitis (inflammation of the spinal cord) Pain and swelling in the large joints (such as knees) Shooting pains that may interfere with sleep Heart palpitations and dizziness due to changes in heartbeat Many of these symptoms will[web.archive.org]


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]
Brucella Abortus
  • Giambartolomei, Brucella abortus Induces the Secretion of Proinflammatory Mediators from Glial Cells Leading to Astrocyte Apoptosis, The American Journal of Pathology, 10.2353/ajpath.2010.090503, 176, 3, (1323-1338), (2010). Tereance A.[doi.org]


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


  • 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 99.2% spontaneous recovery rate demonstrates the unequivocally excellent prognosis of this palsy and confirms that operative intervention is not indicated.[doi.org]


  • 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]
  • 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]
  • An etiological diagnosis of the dementia was made at the end of the follow-up of 5.0 2.9 years.[prohealth.com]
  • Etiology Caused by tick-borne spirochete Borrelia burgdorferi sensu lato. Its passage through the Blood-Brain-Barrier results in Central Nervous System (CNS) infection, causing widespread neurological symptoms 4.[slideshare.net]


  • 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]
Sex distribution
Age distribution


  • An observed decrease in gelsolin concentration in the blood of TBE and LNB patients supports previous findings indicating the involvement of gelsolin in the pathophysiology of an inflammatory response.[ncbi.nlm.nih.gov]
  • CIP is associated with poor quality of life and high morbidity. 3 Pathophysiological aspects of the condition remain obscure and treatment options are limited and often unsatisfactory. 9 Consequently, it is crucial that all physicians and gastroenterologists[jnmjournal.org]
  • Dworkin, Acute and chronic pain associated with Lyme borreliosis: Clinical characteristics and pathophysiologic mechanisms, Pain, 155, 8, (1435), (2014). R. Eikeland, Å. Mygland, K. Herlofson and U.[doi.org]


  • Prompt diagnosis and treatment appear to facilitate symptomatic relief and prevent persistent neurologic deficits.[ncbi.nlm.nih.gov]
  • Centers for Disease Control and Prevention [On-line information]. Available online at . Accessed March 2009. (Reviewed 2008 October 7). Lyme Disease Diagnosis. Centers for Disease Control and Prevention [On-line information]. Available online at .[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]



  1. Hildenbrand P, Craven DE, Jones R, Nemeskal P. Lyme neuroborreliosis: manifestations of a rapidly emerging zoonosis. AJNR Am J Neuroradiol. 2009;30(6):1079-1087.
  2. Centers for Disease Control and Prevention (CDC). Lyme disease-United States, 2003-2005. MMWR Morb Mortal Wkly Rep. 2007;56(23):573-576.
  3. Sinha A, Dietzman T, Ross D, Sulieman S, Fieldston E. Lyme neuroborreliosis: a diagnostic headache. Hosp Pediatr. 2014;4(6):400-404
  4. Subedi S, Dickeson DJ, Branley JM. First report of Lyme neuroborreliosis in a returned Australian traveller. Med J Aust. 2015 Jul 6;203(1):39-40.
  5. Shah SS, Zaoutis TE, Turnquist J, Hodinka RL, Coffin SE. Early differentiation of Lyme from enteroviral meningitis. Pediatr Infect Dis J. 2005;24(6):542-545.
  6. Strle F, Ružić-Sabljić E, Cimperman, J, et al. Comparison of findings for patients with Borrelia garinii and Borrelia afzelii isolated from cerebrospinal fluid. Clin Infect Dis. 2006;43:704-710.
  7. Aguero-Rosenfeld ME, Wang G, Schwartz I, et al. Diagnosis of Lyme borreliosis. Clin Microbiol Rev 2005;18:484–509.
  8. Centers for Disease Control and Prevention. Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 1995;44:590-591.
  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.

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Last updated: 2019-07-11 21:02