http://www.efns.org/fileadmin/user_uplo ... liosis.pdf
Received 7 August 2009
Accepted 2 October 2009
EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis
A°. Mygland a,b,c, U. Ljøstad a, V. Fingerle d, T. Rupprecht e, E. Schmutzhard f and I. Steiner g
a Department of Neurology;
b Department of Rehabilitation, Sørlandet Sykehus, Kristiansand;
c Department of Clinical Medicine, University of Bergen, Bergen, Norway;
d Bavarian Health and Food Safety Authority, Oberschleißheim;
e Department of Neurology, Ludwig-Maximilians University, Munich, Germany;
f Department of Neurology, Medical University Innsbruck, Innsbruck, Austria; and
g Neurological Sciences Unit, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel
Background: Lyme neuroborreliosis (LNB) is a nervous system infection caused by
Borrelia burgdorferi sensu lato (Bb).
Objectives: To present evidence-based recommendations for diagnosis and treatment.
Methods: Data were analysed according to levels of evidence as suggested by EFNS.
Recommendations: The following three criteria should be fulfilled for definite LNB,
and two of them for possible LNB: (i) neurological symptoms; (ii) cerebrospinal fluid
(CSF) pleocytosis; (iii) Bb-specific antibodies produced intrathecally. PCR and CSF
culture may be corroborative if symptom duration is <6 weeks, when Bb antibodies
may be absent. PCR is otherwise not recommended. There is also not enough evidence
to recommend the following tests for diagnostic purposes: microscope-based assays,
chemokine CXCL13, antigen detection, immune complexes, lymphocyte transformation
test, cyst formation, lymphocyte markers. Adult patients with definite or possible
acute LNB (symptom duration <6 months) should be offered a single 14-day course
of antibiotic treatment. Oral doxycycline (200 mg daily) and intravenous (IV) ceftriaxone
(2 g daily) are equally effective in patients with symptoms confined to the
peripheral nervous system, including meningitis (level A). Patients with CNS manifestations
should be treated with IV ceftriaxone (2 g daily) for 14 days and late LNB
(symptom duration >6 months) for 3 weeks (good practice points). Children should
be treated as adults, except that doxycycline is contraindicated under 8 years of age
(nine in some countries). If symptoms persist for more than 6 months after standard
treatment, the condition is often termed post-Lyme disease syndrome (PLDS).
Antibiotic therapy has no impact on PLDS (level A).
Lyme neuroborreliosis (LNB) is an infectious disorder of the nervous system caused by tick-borne spirochetes of the Borrelia burgdorferi (Bb) sensu lato complex. Clinical features of LNB are diverse and differ in European and American patients – most probably because of different bacteria species.
Clinical features of LNB
Neurological symptoms usually occur 1–12 (mostly 4–6) weeks after the tick bite, and mainly from July to December. Only 40–50% of the patients can recall a tick bite, and 20–30% report a local skin infection (erythema migrans) (stage I) [11,12]. More than 95% can be classified as early LNB (stage II), defined as signs and symptoms lasting for <6 months. Less than 5% have late LNB (stage III) with duration between 6 months and several years . The natural course of early LNB is often self-limiting , whereas late LNB has a chronic course that probably reflects persistent survival of bacteria in nervous tissue.
[Table 1 Classification of Lyme neuroborreliosis (LNB)]
Early LNB (Table 1)
PNS manifestations. The most common manifestation of early LNB in Europe is a painful meningoradiculitis (Bannwarths syndrome). The clinical hallmarks of Bannwarths syndrome are radicular pain (in 86% of the patients) and paresis (in 61%) . The pain is generally described as being of a type never experienced before. The intensity and localization of the pain may vary from day to day and typically exacerbates at night. The paresis may affect muscles innervated by cranial nerves (especially the facial nerve, less often the abducens or the oculomotor nerves), the abdominal wall or the limbs. Headache occurs in about 43%, but a prominent headache without radicular pain or paresis is rare in adults. Apart from Bannwarths syndrome and lymphocytic meningitis, other peripheral neurological manifestations (in 5–10% of the patients) are plexus neuritis and mononeuritis multiplex.
CNS manifestations. CNS involvement is rare, but patients may present with myelitis or encephalitis. Clinical manifestations like confusion, cerebellar ataxia, opsoclonus–myoclonus, ocular flutter, apraxia, hemiparesis or Parkinson-like symptoms have been associated with Bb infection . Poliomyelitis-like syndromes , and acute stroke-like symptoms caused by cerebral vasculitis  are rare and have been documented only in single case reports.
Late LNB (Table 1)
Late neurological manifestations are also entitled chronic neuroborreliosis.
PNS manifestations. It may consist of mononeuropathy, radiculopathy and polyneuropathy [17,18]. In Europe, late polyneuropathy has only been observed in combination with acrodermatitis chronica atrophicans (ACA)  – the typical dermatological manifestation during late stage III of borrelial infection – whilst isolated cases of distal symmetric polyneuropathy as a result of a borrelial infection have been reported in American patients . It is of note that a causative relationship between polyneuropathy and borrelial infection cannot be based on the sole detection of Bb specific antibodies in patients with polyneuropathy as those antibodies can also be found in 5–25% of healthy persons .
CNS manifestations. It includes (i) cerebral vasculitis and (ii) chronic progressive Lyme encephalitis or encephalomyelitis with tetraspastic syndrome, spastic–ataxic gait disorder and disturbed micturition .
Differences between European and American LNB
Unlike the European Lyme disease, the North American disorder is characterized by erythema migrans, arthritis and meningitis. It is usually deficient of painful radicular symptoms, other cranial nerve involvement besides the facial nerve and ACA.
The most common manifestations of LNB in European children are acute facial nerve palsy (in 55%), other cranial nerve palsies and lymphocytic meningitis (in 27%) [22,23]. Small children may present with unspecific symptoms such as loss of appetite and fatigue. CNS symptoms are rare, but children with early LNB may present with acute myelitis , acute hemiparesis , opsoclonus–myoclonus  or ataxia . Late LNB with chronic hemiparesis has also been reported .