Sciatica, disk herniation, and neuroborreliosis. A report of four cases

Joint Bone Spine 71 (2004) 433–437 www.elsevier.com/locate/bonsoi

Case report

Sciatica, disk herniation, and neuroborreliosis. A report of four cases Arnaud Dupeyron a,*, Jehan Lecocq a, Benoît Jaulhac b, Marie-Eve Isner-Horobeti a, Philippe Vautravers a, Julien Cohen-Solal c, Christelle Sordet c, Jean-Louis Kuntz c a Physical Medicine and Rehabilitation Unit, Strasbourg Teaching Hospitals, Avenue Molière, 67098 Strasbourg cedex, France School of Medicine, Bacteriology Institute, Louis Pasteur University and Strasbourg Teaching Hospitals, 67000 Strasbourg, France c Rheumatology and Clinical Immunology Department, Strasbourg Teaching Hospitals, Avenue Molière, 67098 Strasbourg cedex, France b

Available online 25 September 2003

Abstract We report four cases of sciatica in patients with same-level disk herniation confirmed by computed tomography and a final diagnosis of acute radiculitis caused by Borrelia burgdorferi, with a favorable response to ceftriaxone therapy. The neurological manifestations of Lyme disease are protean, and a potential contribution of concomitant disk disease to sciatica can lead to diagnostic wanderings. Disk lesions and infectious conditions that can cause sciatica are discussed. Whether a favorable response to antibiotic therapy should be taken as proof of B. burgdorferi radiculitis deserves discussion. In practice, in a patient with clinical manifestations suggesting disk-related nerve root pain and residing or having traveled to an endemic area, B. burgdorferi infection should be looked for, as both etiologies can coexist. © 2003 Elsevier SAS. All rights reserved. Keywords: Neuroborreliosis; Sciatica; Disk herniation; Meningoradiculitis

1. Introduction The neurological manifestations of Lyme disease, a condition caused by the spirochete Borrelia burgdorferi, are protean, the most common in Europe being meningoradiculitis. The considerable diversity of the peripheral neuropathies caused by B. burgdorferi raises major diagnostic challenges. We report four cases of sciatica with same-site disk herniation confirmed by computed tomography, in which failure of appropriate medical treatment led to a reappraisal of the diagnosis. Evidence of neuroborreliosis was found, and antibiotic therapy was effective. The disk herniation may have been a mere coincidence that played no role in the genesis of the nerve root pain. Alternatively, the disk herniation and neuroborreliosis may have interacted to cause the sciatica, perhaps via mutual potentiation or perpetuation. 2. Patients and methods The four patients included in this study had chronic sciatica or femoral neuralgia. Details are provided on findings * Corresponding author. Service de médecine Physique et Réadaptation, Hôpitaux Universitaires de Strasbourg, Avenue Molière, 67098 Strasbourg cedex, France. E-mail address: [email protected] (A. Dupeyron). © 2003 Elsevier SAS. All rights reserved. doi:10.1016/j.jbspin.2003.09.002

from the physical examination, lumbar spine CT, electromyogram (one patient), and laboratory tests (Lyme serology, western blot, PCR [1,2] and HLA type) in these patients. Serological tests for Lyme disease were positive in the blood and cerebrospinal fluid (CSF) in all four patients. We did not obtain direct proof that B. burgdorferi was present because PCR testing for the bacterial DNA was done in only two patients and could not be interpreted, due to presence of an inhibitor in one patient and to a technical problem in the other.

3. Case-reports 3.1. Case 1 This 63-year-old man with an unremarkable medical history was admitted for low back pain and femoral neuralgia on the left side that had started 4 months earlier and failed to respond to medical therapy. He had moderately severe spinal symptoms, L4 neuralgia on the left made worse by coughing, blunting of the left knee reflex, and a positive contralateral straight leg-raising test. No severe motor or sensory loss was found. CT of the lumbar spine showed herniation of the L3–L4 disk on the left and of the L5–S1 disk on the midline.

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Electromyogram (EMG) findings suggested residual impairments from palsy of the left L3 root. Serological tests for Lyme disease were positive in the serum (IgG titer, 20 U, and western blot positive for four proteins) and in the CSF (IgG titer, 25 U, and western blot positive for two proteins); the CSF contained 1.18 g/l protein and 10 cells/mm3 with 40% lymphocytes. The HLA type was DR 01/08, DQ 05/04. Ceftriaxone (2 g/d intramuscularly) was given for 3 weeks. The pain and other clinical manifestations resolved promptly. No further symptoms occurred throughout the 18-month follow-up. 3.2. Case 2 A 43-year-old man with a history of recurrent low back pain was admitted for a 6-month history of S1 sciatica on the left side. The pain had started 6 months earlier, failing to respond to nonsteroidal antiinflammatory drugs, analgesics, and epidural glucocorticoid injections. The low back was normal to physical examination. He had pain in the left S1 distribution and paresthesia in the left leg, without evidence of dura mater involvement or neurological impairment. CT of the lumbar spine disclosed an L5–S1 herniation on the left, as well as thickening of the left L5 root. Serological tests for Lyme disease were positive in the serum (IgG titer, 14 U, and western blot positive for nine proteins) and in the CSF (IgG titer, 20 U, and western blot positive for three proteins); the CSF protein level was 0.90 g/l and there were 3 cells/mm3 with 100% lymphocytes. HLA testing showed the DR 15/03, DQ 06/02 phenotype. Ceftriaxone (2 g/d intramuscularly) given for 3 weeks ensured complete resolution of the pain with no recurrence during the 4-year follow-up. 3.3. Case 3 A 51-year-old man with a history of surgical L5–S1 discectomy for S1 sciatica on the left 5 years earlier was admitted for low back pain and S1 sciatica on the left that had started 6 months earlier. Analgesics and antiinflammatory drugs given orally and by epidural injection had provided no relief. Physical examination showed moderately severe lumbar spine abnormalities and a positive straight leg-raising test at, 45°. Neurological findings were normal. CT of the lumbar spine visualized material of tissue density filling the S1 left lateral recess and consistent with either recurrent herniation or postsurgical fibrosis; in addition, the right S1 root was thickened. Serological tests for Lyme disease were positive in the serum (IgG titer, 120 U, and western blot positive for 11 proteins) and in the CSF (IgG titer, 9 U, and western blot positive for three proteins); the protein level was slightly elevated in the CSF, to 0.60 g/l, but no cells were found. The HLA phenotype was DR 01/07, DQ 05/02. Ceftriaxone (2 g/d intramuscularly) given for 3 weeks ensured slow resolution of the pain within 1 month. At last follow-up 5 years later, the patient remained free of symptoms.

3.4. Case 4 This 46-year-old man with no other history of significant disease underwent L5–S1 discectomy in March 2000 for sciatica on the right. A few months later, he reported sciatica on the left consistent with recurrent herniation, which was confirmed by CT. Despite pharmacotherapy, the pain persisted. After 1 year, he had severe lumbar spine abnormalities upon physical examination with subtle evidence of disk impingement and pain radiating down to the left calf. The straight leg-raising test was positive at 60°. Neurological findings were normal. He reported severe asthenia with aching sensations in the shoulder and hip girdles. Magnetic resonance imaging (MRI) of the lumbar spine was consistent with postsurgical fibrosis in the L5–S1 epidural space, bulging of the disk to the left of the midline and a large increase in the diameter of the right S1 root. Serological tests for Lyme disease were positive in the serum (IgG titer, 195 U, and western blot positive for five proteins) and the CSF (IgG titer, 60 U, and western blot positive for proteins); the CSF protein level was 0.65 g/l and there were 10 cells/mm3 with 60% lymphocytes. HLA testing showed the DR 16/04, DQ 05/03 phenotype. Ceftriaxone (2 g/d intramuscularly) was given for 3 weeks. The sciatica and the aching pain resolved almost completely and the asthenia abated. However, physical examination of the lumbar spine remained abnormal at last follow-up after 6 months. Table 1 recapitulates the main features in these four patients.

4. Discussion Our four patients had chronic radiculitis that failed to respond to appropriate medical treatment for disk-related nerve root pain but improved dramatically with antibiotic therapy. There was usually no clinical evidence of meningeal involvement. None of the patients had a known history of erythema chronicum migrans before or at onset of the nerve root pain. Each of the four patients had a disk herniation at the level of the nerve root pain, but there was no direct evidence that the disk impinged on a root. An EMG performed in one patient showed abnormalities that were taken to indicate moderate sequelae of radiculitis (chronic neurogenic atrophy), although the cause could not be determined. Lyme disease [3] is caused by the spirochete B. burgdorferi, which usually infects animals, humans being occasional hosts. In the United States, over 10 000 new cases are reported each year (including 90% in the north-eastern states). In Europe, the incidence of Lyme disease decreases from the north to the south and from the east to the west, from 5/100 000 in Ireland to 300/100 000 in Austria. In France, the mean incidence is 16.5/100 000 (Alsace in eastern France, 86/100 000), and in Belgium 500 new cases are reported annually [4]. Neurological manifestations related to B. burgdorferi infection in humans were first described in Europe in 1922 [5]. They vary widely, the most common being a com-

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Table 1 Recapitulation of the case reports Cases Nerve root involved Disk herniation visualized by lumbar spine CT

Case 1 L4, left L3–L4, left

Case 2 S1, left L5–S1, left

Case 3 S1, left L5–S1, left

Case 4 S1, right L5–S1, right

Serology (IgG) Blood (units) CSF (units)

20 25

14 20

120 9

195 60

Western blot Blood (number of proteins) CSF (number of proteins)

2 2

9 3

11 3

5 5

CSF Proteins (g/l) Cells (per mm3)

1.18 10

0.90 3

0.60 0

0.65 10

HLA DR HLA DQ Outcome Follow-up duration

01/08 05/04 No pain 18 months

15/03 06/02 No pain 4 years

01/07 05/02 No pain 5 years

16/04 05/03 Marked subsidence of pain 6 months

CT, computed tomography; CSF, cerebrospinal fluid.

bination of meningitis, palsies of cranial nerves (most commonly the facial nerve), and radiculitis (Bannwarth syndrome) [5]. Other common manifestations include isolated motor or sensory polyneuropathy [6,7], mononeuropathy [8], and lymphocytic meningitis [9,10]. In the few reported cases of encephalitis or encephalomyelitis, a causative role for B. burgdorferi was not always firmly established [10–13]. Neurological manifestations occur in 10–40% of patients with Lyme disease [9,14,15]. Meningoradiculitis due to Lyme disease typically starts with pain in the lower limbs that fluctuates in intensity and lasts 5–6 months [16–18]. Antibiotic therapy is usually effective in relieving the pain [19]. It is important to bear in mind that specific antibodies to B. burgdorferi can persist in the CSF independently from the clinical course [20]. Nerve biopsies done in patients with meningoradiculitis showed lymphocytic infiltration of the vasa nervorum without necrosis, suggesting inflammatory neuropathy with secondary wallerian degenerescence [21,22]. Abnormalities by electrophysiological testing usually indicate axonopathy and abate in parallel with the clinical improvement [6,23]. Recent data from a primate model show that neuroborreliosis is due to persistent infection and that presence of the organism is necessary but not sufficient to generate inflammation [27]. In a study of 103 patients with low back pain and nerve root pain, three patients had both a disk herniation and intrathecal production of antibodies to B. burgdorferi, although the absence of acute radiculitis and of a concomitant cellular reaction led the authors to rule out Lyme disease as the cause of the pain [28]. Of our four patients, two had a lymphocytic reaction that was minimal yet strongly suggested a nonmechanical factor. In addition, one of these two patients and one of the patients without a cellular reaction had a meaningful increase in CSF protein levels indicating that disk impingement was not the only cause to the nerve root pain.

The pattern of radiculitis in our patients is consistent with late-stage untreated meningoradiculitis responsible for chronic pain and responding promptly to antibiotic therapy. The patients described the pain as fluctuating in severity but differentiated these fluctuations clearly from the prompt resolution of the pain induced by the antibiotic infusions. This clinical pattern may represent a distinctive course of meningoradiculitis seen more often in Europe than in the United States and perhaps characterized by a smoldering course with a good response to antibiotics. Alternatively, the antibiotic treatment may have been instituted at the end of a bout of sciatica that was resolving spontaneously, the concomitant presence of Lyme disease being a mere coincidence. The refractoriness to treatment for disk-related nerve root pain contrasting with the prompt relief after initiation of antibiotic therapy argues convincingly against this possibility. However, since ceftriaxone is not specific for B. burgdorferi, a role for another organism cannot be ruled out, although no clinical or laboratory test findings suggested a possible culprit other than Lyme disease. Stirling et al. [29] reported several cases of sciatica associated with Proprionibacterium acnes infection manifesting only as positive serological tests and positive cultures of discectomy specimens. The coexistence of a disk herniation in our patients might explain the chronic course of the pain, as mechanical irritation might both perpetuate the inflammatory process due to the infection and generate inflammation. The clinical response to antibiotic therapy militates against this possibility. The disk herniation may act merely as a precipitating factor, explaining why B. burgdorferi affects the root at that level rather than another root. Axonal degenerescence secondary to vascular involvement may be caused either by proliferation of the spirochete in the vasa nervorum of the epineurium (perhaps in the early stages of the infection) or by an indirect

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mechanism involving immune complexes or cross-reactive antibodies [9]. Secondary reactivation of an immunological process (due to a mechanical or infectious factor) may explain the recurrence of the pain. Should this be the case, the pain might be related either to infection by B. burgdorferi via the mechanisms suggested above or to the disk herniation. A role for autoimmunity in symptoms related to disk impingement has been suggested. The nucleus pulposus can cause inflammation of the nerve root, perhaps via the many pathogenic and algogenic substances produced by the nucleus pulposus and perhaps in part via an autoimmune response [30–33]. Boulu and Benoist [30] suggested that neurotoxic substances from the nucleus pulposus may penetrate into the endoneurium capillaries, causing axonal ischemia responsible for nerve root alterations. Similarly, a vascular mechanism has been suggested as the cause of the neurological manifestations seen in borreliosis. Thus, the nerve root alterations induced by disk herniation might create local conditions conducive to infection by B. burgdorferi. Infectious radiculitis caused by B. burgdorferi is probably accompanied with a reaction involving the same pathogenic and algogenic substances.

[3] [4]

Finally, some forms of Lyme disease are associated with genetic susceptibility factors, of which the best known are the combination of HLA-DR4 and the surface proteins OspA and OspB, which are more common in patients with chronic arthritis refractory to antibiotic treatment [24,25] and HLA DR 15/16, which confers an increased risk of neurological manifestations [26]. Three of our four patients carried the DQ 5 antigen, a finding that does not allow any conclusion. (25% in general population)

[13] Fallon BA, Nields JA, Parsons B, Liebowitz MR, Klein DF. Psychiatric manifestations of Lyme borreliosis. J Clin Psychiatry 1993;5: 263–8.

These clinical and laboratory test abnormalities, together with the response to antibiotic therapy, strongly suggest that the distinctive pattern of radiculitis in our patients was related to B. burgdorferi infection. Tests for genetic susceptibility factors might be of interest in our patients. In practice, these four case-reports indicate that B. burgdorferi radiculitis and disk herniation at the same level can coexist. Therefore, testing for B. burgdorferi infection can be useful in patients residing or traveling to endemic areas and presenting with apparently disk-related nerve root pain that fails to respond to treatment for this condition.

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