Lyme Neuroborreliosis: Known Knowns, Known Unknowns

John J. Halperin; Randi Eikeland; John A. Branda; Rick Dersch

Disclosures

Brain. 2022;145(8):2635-2647. 

In This Article

Clinical

General

The earliest sign of Bbsl infection is typically EM, usually developing days to weeks after infection, in contrast to the virtually immediate local allergic reaction to tick saliva. EM represents an inflammatory reaction to local spirochete proliferation and centrifugal migration. Typically 5+ cm in diameter EM expands day by day, often to an impressive size, despite which it is often asymptomatic. Consequently, it may go unnoticed if in difficult to visualize anatomic locations. Infection may remain localized or may disseminate—the latter often accompanied by typical systemic symptoms of infection—arthralgias, myalgias, headache. Dissemination may lead to multiple secondary EMs—each recapitulating the evolution of the initial one. Cardiac involvement is infrequent[20] (~1%) but can result in symptomatic heart block. Untreated patients may subsequently develop Lyme arthritis—particularly with Bbss.

Neurological Manifestations

In both Europe and the USA, the most common presentations involve various combinations of lymphocytic/monocytic meningitis, cranial neuropathy and radiculoneuritis (Table 2 and Table 3), typically occurring early in infection. Meningitis symptoms vary widely, from minimal, to severe headaches with photosensitivity and neck stiffness. Facial nerve involvement represents 80% of cranial neuropathies and can be bilateral—concurrently or in rapid succession. Radiculoneuropathy classically causes severe, dermatomal neuropathic pain, comparable to that seen in mechanical, diabetic or zoster radiculopathies. Sensory symptoms often extend beyond a single dermatome; muscle weakness and atrophy may develop in the affected nerve distribution. PNS involvement can include brachial or lumbosacral plexopathies, more localized mononeuropathies or a mononeuropathy multiplex.

Reported frequencies of neurologic manifestations vary among different populations. In the USA, ~60% of diagnosed LNB patients develop facial palsy, 30% radiculoneuropathy, 10% isolated meningitis.[20] In Europe, among adults, frequencies of facial palsy and radiculoneuropathy are the reverse;[61] in children[79–82] headache is the most frequent symptom, FNP the most common finding (46%), radiculoneuropathy very infrequent. Long term prognosis appears to be comparably favorable in adults and children.[81] A particular concern, primarily in children, is that LNB can cause a pseudotumour cerebri-like picture. Most such patients have a CSF pleocytosis,[83] suggesting a pathophysiology different from idiopathic intracranial hypertension; however severe visual impairment can ensue, so recognition and specific treatment are essential. Overall incidence of LNB[84] appears to have declined in recent years, at least in Denmark, perhaps reflecting earlier Lyme borreliosis recognition and treatment, more accurate LNB diagnosis, or both.

European patients may develop a late cutaneous manifestation, ACA, diagnosed rarely if ever in North America, while US patients more frequently develop frank arthritis—differences attributed to differing Bbsl strains. Patients with these late extraneurological manifestations may develop a more indolent and disseminated mononeuropathy multiplex, often with normal CSF[36,60] exemplifying a common diagnostic challenge. While PNS involvement accompanied by inflammatory CSF can readily meet criteria for possible or definite LNB (Table 2), given the high prevalence of seropositivity in endemic areas[36,85,86] seropositive patients with PNS disease and normal CSF must be diagnosed based on other, more characteristic features such as ACA, facial palsy, or otherwise unexplained radiculoneuropathy following an identified tick bite or EM. In such circumstances treatment for LNB may be reasonable, but as always, appropriate alternative diagnoses must be carefully considered, to avoid misattributing a neuropathy to incidental, irrelevant seropositivity.

Finally, parenchymal CNS involvement occurs infrequently—primarily a myelopathy at the involved root level in GBBS. Described as occurring in about 4%[61,87] of European LNB, a recent study found it in just 1/134 patients with definite LNB.[19] Regardless of frequency, since parenchymal CNS involvement represents an infectious myelitis or encephalomyelitis, CSF should be consistently diagnostic. Diagnosing parenchymal CNS LNB absent CSF inflammation and ITAb is problematic.

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