pleocytosis, i.e. the densities of lymphocytes (infection-fighting cells) and protein in the cerebrospinal fluid (csf) typically rise to characteristically abnormal levels, while glucose level remains normal. additionally, the immune system produces antibodies against lyme inside the intrathecal space, which contains the csf. demonstration by lumbar puncture and csf analysis of pleocytosis and intrathecal antibody production are required for definite diagnosis of neuroborreliosis in europe (except in cases of peripheral neuropathy associated with acrodermatitis chronica atrophicans, which usually is caused by borrelia afzelii and confirmed by blood antibody tests). in north america, neuroborreliosis is caused by borrelia burgdorferi and may not be accompanied by the same csf signs; they confirm a diagnosis of central nervous system (cns) neuroborreliosis if positive, but do not exclude it if negative. american guidelines consider csf analysis optional when symptoms appear to be confined to the peripheral nervous system (pns), e.g. facial palsy without overt meningitis symptoms. unlike blood and intrathecal antibody tests, csf pleocytosis tests revert to normal after infection ends and therefore can be used as objective markers of treatment success and inform decisions on whether to retreat. in infection involving the pns, electromyography and nerve conduction studies can be used to monitor objectively the response to treatment. in lyme carditis, electrocardiograms are used to evidence heart conduction abnormalities, while echocardiography may show myocardial dysfunction. biopsy and confirmation of borrelia cells in myocardial tissue may be used in specific cases but are usually not done because of risk of the procedure. polymerase chain reaction (pcr) tests for lyme disease have also been developed to detect the genetic material (dna) of the lyme disease spirochete. culture or pcr are the current means for detecting the presence of the organism, as serologic studies only test for antibodies of borrelia. pcr has the advantage of being much faster than culture. however, pcr tests are susceptible to false positive results, e.g. by detection of debris of dead borrelia cells or specimen contamination. even when properly performed, pcr often shows false-negative results because few borrelia cells can be found in blood and cerebrospinal fluid (csf) during infection. hence, pcr tests are recommended only in special cases, e.g. diagnosis of lyme arthritis, because it is a highly sensitive way of detecting ospa dna in synovial fluid. although sensitivity of pcr in csf is low, its use may be considered when intrathecal antibody production test results are suspected of being falsely negative, e.g. in very early (< 6 weeks) neuroborreliosis or in immunosuppressed people. several other forms of laboratory testing for lyme disease are available, some of which have not been adequately validated. ospa antigens, shed by live borrelia bacteria into urine, are a promising technique being studied. the use of nanotrap particles for their detection is being looked at and the ospa has been linked to active symptoms of lyme. high titers of either immunoglobulin g (igg) or immunoglobulin m (igm) antibodies to borrelia antigens indicate disease, but lower titers can be misleading, because the igm antibodies may remain after the initial infection, and igg antibodies may remain for years. the cdc does not recommend urine antigen tests, pcr tests on urine, immunofluorescent staining for cell-wall-deficient forms of b. burgdorferi, and lymphocyte transformation tests. imaging neuroimaging is controversial in whether it provides specific patterns unique to neuroborreliosis, but may aid in differential diagnosis and in understanding the pathophysiology of the disease. though controversial, some evidence shows certain neuroimaging tests can provide data that are helpful in the diagnosis of a person. magnetic resonance imaging (mri) and single-photon emission computed tomography (spect) are two of the tests that can identify abnormalities in the brain of a person affected with this disease. neuroimaging findings in an mri include lesions in the periventricular white matter, as well as enlarged ventricles and cortical atrophy. the findings are considered somewhat unexceptional because the lesions have been found to be reversible following antibiotic treatment. images produced using spect show numerous areas where an insufficient amount of blood is being delivered to the cortex and subcortical white matter. however, spect images are known to be nonspecific because they show a heterogeneous pattern in the imaging. the abnormalities seen in the spect images are very similar to those seen in people with cerebral vasculitis and creutzfeldt–jakob disease, which makes them questionable. differential diagnosis community clinics have been reported to misdiagnose 23–28% of erythema migrans (em) rashes and 83% of other objective manifestations of early lyme disease. em rashes are often misdiagnosed as spider bites, cellulitis, or shingles. many misdiagnoses are credited to the widespread misconception that em rashes should look like a bull's eye. actually, the key distinguishing features of the em rash are the speed and extent to which it expands, respectively up to 2–3 cm/day and a diameter of at least 5 cm, and in 50% of cases more than 16 cm. the rash expands away from its center, which may or may not look different or be separated by ring-like clearing from the rest of the rash. compared to em rashes, spider bites are more common in the limbs, tend to be more painful and itchy or become swollen, and some may cause necrosis (sinking dark blue patch of dead skin). cellulitis most commonly develops around a wound or ulcer, is rarely circular, and is more likely to become swollen and tender. em rashes often appear at sites that are unusual for cellulitis, such as the armpit, groin, abdomen, or back of knee. like lyme, shingles often begins with headache, fever, and fatigue, which are followed by pain or numbness. however, unlike lyme, in shingles these symptoms are usually followed by appearance of rashes composed of multiple small blisters along with a nerve's dermatome, and shingles can also be confirmed by quick laboratory tests. facial palsy caused by lyme disease (ldfp) is often misdiagnosed as bell's palsy. although bell's palsy is the most common type of one-sided facial palsy (about 70% of cases), ldfp can account for about 25% of cases of facial palsy in areas where lyme disease is common. compared to ldfp, bell's palsy much less frequently affects both sides of the face. even though ldfp and bell's palsy have similar symptoms and evolve similarly if untreated, corticosteroid treatment is beneficial for bell's palsy, while being detrimental for ldfp. recent history of exposure to a likely tick habitat during warmer months, em rash, viral-like symptoms such as headache and fever, and/or palsy in both sides of the face should be evaluated for the likelihood of ldfp; if it is more than minimal, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for lyme disease. unlike viral meningitis, lyme lymphocytic meningitis tends to not cause fever, last longer, and recur. lymphocytic meningitis is also characterized by possibly co-occurring with em rash, facial palsy, or partial vision obstruction and having much lower percentage of polymorphonuclear leukocytes in csf. lyme radiculopathy affecting the limbs is often misdiagnosed as a radiculopathy caused by nerve root compression, such as sciatica. although most cases of radiculopathy are compressive and resolve with conservative treatment (e.g., rest) within 4–6 weeks, guidelines for managing radiculopathy recommend first evaluating risks of other possible causes that, although less frequent, require immediate diagnosis and treatment, including infections such as lyme and shingles. a history of outdoor activities in likely tick habitats in the last 3 months possibly followed by a rash or viral-like symptoms, and current headache, other symptoms of lymphocytic meningitis, or facial palsy would lead to suspicion of lyme disease and recommendation of serological and lumbar puncture tests for confirmation. lyme radiculopathy affecting the trunk can be misdiagnosed as myriad other conditions, such as diverticulitis and acute coronary syndrome. diagnosis of late-stage lyme disease is often complicated by a multifaceted appearance and nonspecific symptoms, prompting one reviewer to call lyme the new "great imitator". as all people with later-stage infection will have a positive antibody test, simple blood tests can exclude lyme disease as a possible cause of a person's symptoms. prevention tick bites may be prevented by avoiding or reducing time in likely tick habitats and taking precautions while in and when getting out of one. most lyme human infections are caused by ixodes nymph bites between april and september. ticks prefer moist, shaded locations in woodlands, shrubs, tall grasses and leaf litter or wood piles. tick densities tend to be highest in woodlands, followed by unmaintained edges between woods and lawns (about half as high), ornamental plants and perennial groundcover (about a quarter), and lawns (about 30 times less). ixodes larvae and nymphs tend to be abundant also where mice nest, such as stone walls and wood logs. ixodes larvae and nymphs typically wait for potential hosts ("quest") on leaves or grasses close to the ground with forelegs outstretched; when a host brushes against its limbs, the tick rapidly clings and climbs on the host looking for a skin location to bite. in northeastern united states, 69% of tick bites are estimated to happen in residences, 11% in schools or camps, 9% in parks or recreational areas, 4% at work, 3% while hunting, and 4% in other areas. activities associated with tick bites around residences include yard work, brush clearing, gardening, playing in the yard, and letting into the house dogs or cats that roam outside in woody or grassy areas. in parks, tick bites often happen while hiking or camping. walking on a mowed lawn or center of a trail without touching adjacent vegetation is less risky than crawling or sitting on a log or stone wall. pets should not be allowed to roam freely in likely tick habitats. as a precaution, cdc recommends soaking or spraying clothes, shoes, and camping gear such as tents, backpacks and sleeping bags with 0.5% permethrin solution and hanging them to dry before use. permethrin is odorless and safe for humans but highly toxic to ticks. after crawling on permethrin-treated fabric for as few as 10–20 seconds, tick nymphs become irritated and fall off or die. permethrin-treated closed-toed shoes and socks reduce by 74 times the number of bites from nymphs that make first contact with a shoe of a person also wearing treated shorts (because nymphs usually quest near the ground, this is a typical contact scenario). better protection can be achieved by tucking permethrin-treated trousers (pants) into treated socks and a treated long-sleeve shirt into the trousers so as to minimize gaps through which a tick might reach the wearer's skin. light-colored clothing may make it easier to see ticks and remove them before they bite. military and outdoor workers' uniforms treated with permethrin have been found to reduce the number of bite cases by 80–95%. permethrin protection lasts several weeks of wear and washings in customer-treated items and up to 70 washings for factory-treated items. permethrin should not be used on human skin, underwear or cats. the epa recommends several tick repellents for use on exposed skin, including deet, picaridin, ir3535 (a derivative of amino acid beta-alanine), oil of lemon eucalyptus (ole, a natural compound) and ole's active ingredient para-menthane-diol (pmd). unlike permethrin, repellents repel but do not kill ticks, protect for only several hours after application, and may be washed off by sweat or water. the most popular repellent is deet in the u.s. and picaridin in europe. unlike deet, picaridin is odorless and is less likely to irritate the skin or harm fabric or plastics. repellents with higher concentration may last longer but are not more effective; against ticks, 20% picaridin may work for 8 hours vs. 55–98.11% deet for 5–6 hours or 30–40% ole for 6 hours. repellents should not be used under clothes, on eyes, mouth, wounds or cuts, or on babies younger than 2 months (3 years for ole or pmd). if sunscreen is used, repellent should be applied on top of it. repellents should not be sprayed directly on a face, but should instead be sprayed on a hand and then rubbed on the face. after coming indoors, clothes, gear and pets should be checked for ticks. clothes can be put into a hot dryer for 10 minutes to kill ticks (just washing or warm dryer are not enough). showering as soon as possible, looking for ticks over the entire body, and removing them reduce risk