Comparison of Lyme Disease in the United States and Europe

Adriana R. Marques; Franc Strle; Gary P. Wormser


Emerging Infectious Diseases. 2021;27(8):2017-2024. 

In This Article

Neurologic Manifestations

The typical presentation of early Lyme neuroborreliosis is cranial nerve palsy, particularly facial nerve palsy, as well as lymphocytic meningitis and painful radiculitis. In the United States, the most common manifestation of early Lyme neuroborreliosis is facial palsy. Most cases of early Lyme neuroborreliosis in Europe are caused by B. garinii and B. bavariensis; in adult patients, painful meningoradiculitis is most common.[19,20] In a study of 194 adult patients with Lyme neuroborreliosis in Denmark during 2015–2017, radicular pain affected 70% of the patients and facial nerve palsy 43%; intrathecal production of IgG or IgM against Lyme borrelia was found in 87%.[21] Similar results were found in a retrospective series of 431 Lyme neuroborreliosis patients in Denmark, which included 126 children. Radicular pain (in 66%) and facial nerve palsy (in 41%) were the predominant symptoms; 84.5% of patients had evidence of intrathecal antibody production against Lyme borrelia.[22] Although there are no comparable studies from the United States, it seems that adult US patients with early Lyme neuroborreliosis less frequently have severe radicular pain[23] (Table 3). Newer studies addressing Lyme neuroborreliosis in the United States would be a welcome addition for providing additional data on the frequency of particular symptoms and also on clarifying the frequency of intrathecal antibody production to B. burgdorferi s.s. at the time of symptom onset.

Late Lyme neuroborreliosis with encephalitis, myelitis, or encephalomyelitis has been reported in Europe but is very rare in the United States.[24] On the other hand, 2 neurologic manifestations that have been reported to occur in the United States are now regarded as controversial. The first is Lyme encephalopathy, a poorly defined entity, which occurs in the absence of cerebrospinal fluid pleocytosis, intrathecal production of antiborrelial antibody, or direct microbiologic evidence of B. burgdorferi s.s. infection in the central nervous system. Symptoms include memory and concentration complaints. A now-recognized source of confusion with regard to this entity is that some patients with posttreatment Lyme disease syndrome in the United States report cognitive difficulties, and a subset of these patients have abnormal neurocognitive test results.[25,26] Adding to the controversy, however, is the question of what constitutes dysfunction on such testing and the clinical significance of the test results.[27]

The second controversial neurologic manifestation in the United States is a chronic distal symmetric sensory neuropathy. In Europe, distal axonal neuropathy in the context of Lyme disease is exclusively associated with ACA. In patients with ACA, the neuropathy is predominantly sensory, most often in the involved skin areas.[28] Case series in adult patients in the United States reported a similar neuropathy but without evidence of ACA.[29,30] The distribution of neurologic deficits, which is predominantly sensory, is distal and typically symmetric, but it can be asymmetric. The neuropathy is primarily axonal and thought to be a mononeuropathy multiplex, which can be confluent.[24] Cerebrospinal fluid examination is usually unremarkable. Major concerns have been raised as to whether this entity has been appropriately validated as a manifestation of B. burgdorferi s.s. infection in the United States.[31]

Overall, several factors have probably contributed to the belief that cognitive complaints or a chronic distal symmetric sensory peripheral neuropathy was attributable to Lyme disease in the United States.[31] These factors include the use of diagnostic testing that is no longer considered valid, failure to appreciate that background seropositivity for antibodies to B. burgdorferi s.s. exists, and failure to include matched controls to determine if an association with cognitive complaints or peripheral neuropathy with a positive diagnostic assay for Lyme disease is higher than expected.