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Lyme Disease:  The Great Imitator

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Lyme Disease:  The Great Imitator

T. White

Chronic Lyme disease, neuroboreliosis, is an inflammatory disease of the central nervous system (CNS). It is caused by the spirochete Borrelia burgdorferi and introduced into humans through a bite from an infected deer tick (Bransfield, n.d.; Muraro, Wandinger, Bielekova, Gran, Marques, Utz, McFarland, Jacobson & Martin, 2003; Romi, Krakenes, Aarli & Tysnes, 2004). Once it enters the human host, this gram negative bacterium swims through the blood stream until it is able to attach its tip end to an endothelial cell junction. The bacterium then boars between the cells creating an inflammation and irritation that causes the cell to release digestive protein which ultimately creates holes in the capillary bed (Grier, 2005). Through this maneuver, the B. burgdorferi spirochetes permeate the blood-brain barrier and gain access to the spinal cord, brain stem, and brain. Once entrenched, these organisms suppress the propagation of B cells and restrict T cell production of interleukin-2 all the while baracading themselves in cysts created by surrounding fibroblast reactions. This self encapsulation protects the B. burgdorferi spirochete from immune cells and some antibiotics (Stein, Solvason, Biggart & Spiegel, 1996). Within the brain, B. burgdorferi affects cerebral vessels reducing blood flow thus inducing hypoxia to that region of cerebral tissue. 

Lyme disease, like its cousin syphilis, has been called “the great imitator” because it can mimic any disease. It has been said that “to know syphilis is to know medicine” and this is also the case with Lyme disease (Bransfield, n.d.; Crist, n.d.). Initially, Lyme can produce a skin lesion called an erythema migrans at the site of the tick bite accompanied by a low grade fever, headache, stiff neck, fatigue, and joint discomfort. This stage can last for weeks but many patients experience none of these initial symptoms. Within a few weeks or a few months, neurologic symptoms can occur such as Bell’s palsy (a paralysis of one or both sides of the face) and radiculoneuritis (peripheral nerve inflammation with radiating pain). Cardiac symptoms such as palpitations, arrhythmias, and fainting can also become problematic during this second phase (Barbour, 1988; Steere, 2003). Months to sometimes years after the initial introduction of B. burgdorferi, neuroboreliosis begins to manifest itself as the third or final stage of Lyme progression. This stage is characterized by both central cerebral and spinal cord dysfunctions and is often misdiagnosed as a psychiatric disorder. Patients with neuroboreliosis can present with short-term memory loss, panic attacks, anxiety, depression, impulsivity, paranoia, obsessive compulsions, mood lability, and psychotic episodes (Fallon, Das, Plutchok, Tager, Liegner & Van Heertum, 1997; Iero, Elia, Cosentino, Lanuzza, Spada, Toscano, Tripodi, Belfiore & Ferri, 2003; Romi et al., 2004). 

So how does a primary care physician differentiate between Lyme disease and some other psychological abnormality? Fallon et al. (1997) offers five questions to be considered during the initial diagnostic process. First, does the patient have physiological symptoms not associated with a psychological illness such as: headache, erythema migans rash, photo or phonophobia, short term memory loss, or cranial nerve malfunctions? Secondly, is the presenting psychiatric condition within itself unusual? Within the depression, are there episodes of marked mood lability or as with a panic attack; does the attack last for longer than the usual ten minutes? Next, does the patient show little clinical improvement in symptoms when treated with medications that have been effective for this patient in the past? Fourthly, is this psychological abnormality something new to this patient with no identifiable stressors that could have triggered this condition? Lastly, in the patient’s history or family history is there any incidence of psychiatric disturbances that could account for this current condition? Fallon et al. emphasizes that, as a rule of thumb, whenever a patient over the age of 40 experiences a psychiatric disturbance for the first time that appears not to be related to patient history, family history, or environmental stressors, a physiological source must be considered.

Because of the complexity of Lyme disease, a multifaceted approach must be taken in order to correctly diagnose Lyme especially the third stage of neuroboreliosis. The primary care physician will need to conduct a thorough medical history, a mental status exam, neurological evaluation, and physical examination (Bransfield, n.d.). Clinically significant memory problems may not be evident during a routine office visit but neuropsychological testing can reveal them. Tests such as the Wechsler Memory Scale, the Buschke Selective Reminding test, and the Controlled Oral Word Association are extremely helpful assessment instruments (Fallon et al., 1997). Laboratory test results can be conflicting and confusing (Cutler, 1996). The enzyme linked immunosorbent assay (ELISA) is most often the initial blood evaluation conducted. If the ELISA test yields a positive reading for antibodies to B. burgdorferi, a follow-up immunoglobulin test is conducted known as a Western blot test. This second test identifies proteins of the B. burgdorferi spirochete to which antibody response is intended (Shaddick, Phillips, Logigian, Steere, Kaplan, Berardi, Duray, Larson, Wright, Ginsburg, Katz & Liang, 1994; Steere, 2003). Unfortunately, the ELISA test is known to yield false-positive results when searching for antibodies to the B. burgdorferi spirochete because this bacterium shares some common cross-reactive proteins with other diseases (Steere, 2003). Additionally, all serological analysis may be either negative or inconclusive especially during the initial phase of Lyme disease (Karlsson, Hovind-Hougen, Svenungsson & Stiernstedt, 1990). 

Immunoglobulin M (IgM), usually the first responder, cannot be identified during the first couple weeks of the infection. It is not until sometime between the third to sixth weeks of infection that IgM can be detected. Immunoglobulin G (IgG) levels increase even slower than do IgM levels with IgG unidentifiable for four to six weeks after the initial exposure to B. burgdorferi (Barbour, 1988; Craft, Flecher, Shimemoto & Steere, 1986). An ELISA and Western blot can be conducted on cerebrospinal fluid (CSF) samples but the same possible false readings can occur early on. By the third stage, laboratory testing data are typically more conclusive. Blood analysis tends to show elevated levels of IgG and IgM antibodies while CSF analysis shows an abnormally large number of lymphocytes, an elevated protein level, and evidence of intrathecal (the space under the arachnoid membrane in the brain or spinal cord) produced B. burgdorferi antibodies as determined by comparing the CSF/serum ratio of ELISA identified IgG antibodies to B. burgdorferi with the CSF/serum ratio of total IgG (Kirchner, Koedel, Fingerle, Paul, et al., 2000; Meurs, Labeye, Declercq, Pieret & Gille, 2004; Walther, Seelos, Bise, Mayer & Staube, 2004). Neuroimaging test such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the best evaluation of the brain’s functioning, i.e. glucose metabolism and blood flow, when evaluating a patient for neuroboreliosis. SPECT scanning, which is more often available and less expensive than PET scanning, typically shows multiple areas of decreased blood flow in both the cortex and the subcortical white matter. The regions most often affected are the frontal, temporal, and parietal lobes (Cowley & Underwood, 2006; Fallon et al., 1997). It is perhaps this decreased perfusion and its resulting hypoxia that produces the psychological abnormalities so often associated with chronic progressive Lyme disease in its final stage.

Early diagnosis and successful treatment of Lyme disease is paramount to preclude more extensive, often irreparable, tissue damage. Paradoxically, Lyme is easier diagnosed in its later stages than in the initial stage. Early Lyme disease is best treated with oral antibiotics, usually doxycycline (100 mg bid) or amoxicillin (500 mg tid), for two to three weeks. Late stage Lyme or neuroboreliosis must be aggressively treated with intravenous administered antibiotics, most often ceftriaxone (2 g once a day) for one month to six weeks (Logigian, Kaplan & Steere, 1999; Nields, Fallon & Jastreboff, 1999; Steere, 2003; Wormser, Nadelman, Dattwyler, Dennis, Shapiro, Steere, Rush, Rahn, Coyle, Persing, Fish & Luft, 2000). Recovery is slow and some neuroboreliosis patients continue to have ongoing symptoms such as fatigue, muscle pain, joint pain, abnormal tactile sensations, or memory and mood disturbances which may be due to permanent tissue damage ( Stanek & Strle, 2003). Wormser et al. (2000) reports that currently there is no convincing data to support the prolonged or repeated use of antibiotic treatment in cases of symptom resistant neuroborreliosis.

In researching information for this paper, I was amazed to learn that the bite of a tick no larger than the period at the end of this sentence could be a host to such an insidious bacteria. Equally amazing was the fact that immediate removal of an infected attached tick will, in most all cases, prevent one from contracting Lyme disease. In order for the infected tick to transfer the B. burgdorferi bacteria from its gut to its saliva and thus into the human host, the tick must be attached for 24 to 48 hours (Steere, 2003; Wormser et al., 2000).


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