A problematic aspect of Lyme disease relates to the development in some patients of a mild chronic encephalopathy coupled with fatigue. That such a disorder may occur after a well-documented attack of Lyme disease is undoubted. However, in the absence of a history of the characteristic rash, arthritis, or aseptic meningitis, the attribution to Lyme disease of fatigue alone or various other vague mental symptoms, such as difficulty in concentration, is almost always erroneous, even if there is serologic evidence of exposure to the spirochete. It would be an understatement that a large number of patients are persuaded that various symptoms are the result of Lyme infection and seek and receive unnecessary treatment. A comment is made below about imaging findings in Lyme.
In acute and subacute cases that involve the spinal or cranial nerve roots or spinal cord, the CSF routinely shows a pleocytosis (20 to 250 lymphocytes/mm3) with moderately elevated protein; the glucose concentration is usually normal but may be slightly depressed. The majority of cases with facial palsy alone is associated with this CSF formula, but there are exceptions.
Serologic tests are of great value but must be interpreted with caution if there has not been an inciting clinical syndrome of erythema migrans or arthritis or a well-documented tick bite. The most valuable initial screening is performed by the ELISA; if both acute and convalescent sera are tested, approximately 90 percent of patients have a positive IgM response. After the first few weeks, most patients have elevated IgG antibody responses to the spirochete (Berardi et al); a positive test of this nature may simply reflect prior exposure. The ratio of IgG intrathecal anti-Borrelia antibody to that of the serum is greater than 2 in cases of neuroborreliosis; this elevated ratio is a necessary criterion for the diagnosis in Europe. However, Blanc and colleagues studied a sample of 123 consecutive patients with clinical signs of neurologic involvement and found the sensitivity of the index was only 75 percent and the specificity was 97 percent. These authors have proposed more pragmatic diagnostic, but somewhat contrived, criteria for neuroborreliosis, consisting of the presence of 4 of the following 5 items: no past history of neuroborreliosis to explain positive serology, active CSF ELISA serology, anti-Borrelia antibody index greater than 2, favorable outcome after specific antibiotic treatment, and no alternative diagnosis. False-positive tests do occur in some of the conditions that react to syphilitic reagin;
B. burgdorferi–specific antibodies can also be demonstrated in the CSF (these are also reflected by the presence of oligoclonal bands).
Positive ELISA testing should be pursued further with Western blot or immunoblot analysis or other more specific serologies in clinically uncertain cases. Although these latter tests are difficult to carry out and have not been entirely standardized, the presence of both IgG and IgM antibodies is strongly supportive of a recent infection, whereas the IgG is useful in later cases. These laboratory diagnostic issues are discussed and put in perspective by Steere and colleagues (2016). If the European variety of borreliosis is suspected, different serologic tests are required but the general principles of diagnosis are the same as for cases in the United States and elsewhere.
In only approximately 30 percent of cases, the organism can be detected in the spinal fluid using PCR techniques, usually early in the neurologic illness. There are no characteristic imaging findings for neuroborreliosis. In some acute cases one may find enhancement of an affected cranial nerve or spinal nerve root. In the chronic phase of the disease, CT and MRI may display multifocal and periventricular cerebral lesions but these are not specific to Lyme disease, as they also appear in numerous other conditions. The relationship of these lesions, when they do occur in Lyme, to encephalopathy, is unproved.