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Unilateral phrenic nerve lesion in Lyme neuroborreliosis
© Djukic et al.; licensee BioMed Central Ltd. 2013
Received: 27 June 2012
Accepted: 10 January 2013
Published: 18 January 2013
Among a variety of more common differential diagnoses, the aetiology of acute respiratory failure includes Lyme neuroborreliosis.
We report an 87-years old huntsman with unilateral phrenic nerve palsy as a consequence of Lyme neuroborreliosis.
Although Lyme neuroborreliosis is a rare cause of diaphragmatic weakness, it should be considered in the differential workup because of its potentially treatable nature.
Lyme neuroborreliosis (LNB) is the neurological manifestation of the systemic infection caused by the spirochete Borrelia burgdorferi (BB) sensu lato. Clinical features of LNB are diverse and differ among European and American patients, most probably because of differences in the distribution of Borrelia species in Europe and North America [1, 2]. The most common neurological manifestation of LNB in European adults is polyradiculoneuritis (Bannwarth’s syndrome) , which typically occurs in patients older than 50 years, while in younger patients a meningitic syndrome of LNB is common . Although several studies indicate that severe paralysis may occur in LNB , diaphragmatic weakness as a symptom of LNB is rare . Here we report a case of LNB leading to a reduction of vital capacity and severe dyspnoea as a consequence of unilateral paralysis of the diaphragm.
An 87-years old huntsman presented with severe headache, shooting left-sided thoracic pain, fatigue and vertigo. Neurological examination revealed partial dysfunction of the right abducens nerve. During the course of the disease a right facial palsy, with dysarthria and dysphagia as a consequence of facial weakness developed. Although the patient reported multiple previous tick bites, he had never noticed an erythema migrans. Brain magnetic resonance imaging (MRI) without and with contrast medium was unremarkable. The cerebrospinal fluid (CSF) analysis revealed a lymphocytic pleocytosis (129 cells/μl), an elevated lactate level of 2,6 mmol/l, a protein level of 1324 mg/l and an intrathecal Borrelia burgdorferi (BB)-IgG antibodies synthesis (BB-specific antibody index for IgG 5.0 and for IgM 0.8). BB-PCR of CSF was negative. The negative CSF PCR for BB-specific DNA does not exclude the diagnosis, as the sensitivity of PCR in LNB is very low .
Six months later, the patient had no dyspnoea at rest but continued to be short of breath on exertion. Repeat fluoroscopic examination showed partial recovery of the diaphragmatic weakness (Figure 1B). The abducens nerve palsy had recovered completely, but a mild facial palsy remained.
Lyme borreliosis may involve all parts of the nervous system  with as many as 15–20% of infected patients developing neurological symptoms . These usually occur in the first three months following the infection. Diaphragmatic weakness has been associated with trauma, malignant compression or infiltration, metabolic, inflammatory and other disorders, but rarely with Lyme disease . Early recognition and appropriate treatment of diaphragmatic paralysis caused by BB is important in order to shorten the duration of severe respiratory symptoms .
Unilateral diaphragmatic paralysis is a respiratory disorder, and many neurological diseases, such as spinal cord injury, motor neuron disease, and carcinomatous infiltration of the phrenic nerve are included in its differential diagnosis . The development of respiratory compromise due to peripheral nerve involvement in patients with LNB is rare. To our knowledge, only 8 such patients have been described in the literature [7, 9–13]. The severity of the respiratory involvement varies from mild symptoms to the need for artificial ventilation for several months [7, 13]. In the last published report, as many as three patients with diaphragmatic weakness caused by LNB presented over a one-year period. This suggests that the incidence of LNB as a cause of diaphragmatic weakness is underestimated .
Diaphragmatic weakness in LNB results from radiculopathy of the nerve roots C3-C5 or neuropathy of the phrenic nerve . The pathogenesis of the nervous system involvement is uncertain: both direct infection with stimulation of Toll-like receptors  as well as immunological mechanisms with stimulation of T- and B-cells  may play a role.
As in the present case, the clinical diagnosis of LNB is based on a combination of history, typical clinical symptoms, the detection of BB antibodies in serum and CSF and calculation of the BB-specific antibody index . BB antibody tests in serum may be negative in early infection. Conversely, serum antibodies against BB are detectable in up to 25% of healthy persons in Europe . In some patients, antibodies against BB may be detectable in CSF slightly earlier than in serum . Both BB-specific antibodies in serum and BB-specific intrathecal antibody synthesis can persist for years after eradication of the infection . In recent years, the B lymphocyte chemoattractant chemokine CXCL13 has been identified as a potentially important biomarker for the diagnosis of acute LNB [18, 19]. CXCL13, however, seems to be the major determinant for B cell recruitment to the CNS compartments in different neuroinflammatory diseases and not just in LNB . CXCL13 levels in the CSF rather reflect a strong humoral immune response in the CNS compartments than being specific for a particular disease entity .
The marked inflammatory response in CSF (lymphopleocytosis and production of BB-specific antibodies and the absence of other causes) indicate an acute Lyme neuroborreliosis as the reason for respiratory failure in the present case. Irrespective of appropriate antibiotic therapy, diaphragmatic dysfunction in our patient persisted for a long period. Treatment with adequate antimicrobial regimens is usually effective in LNB  but some symptoms may persist longer despite antibiotic treatment, and the recovery can be incomplete [22–24].
LNB should be considered in the differential diagnosis of acute respiratory failure due to diaphragmatic paralysis since it requires adequate antibiotic treatment. It is important in clinical practice to consider Lyme neuroborreliosis also in patients presenting with respiratory failure as an isolated syndrome.
Written informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Series Editor of this journal.
This study was supported and funded by the Robert Bosch Foundation (to M. Djukic) and by the Else Kröner-Fresenius-Stiftung (to R.Nau).
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