Vasculitic mononeuritis multiplex in patient with Lyme ... ies and mononeuritis multiplex as single entities ... Manual muscle testing revealed a marked loss of.
ltal. J. Neurol. Sci. 12:229-232, 1991
Vasculitic mononeuritis multiplex in patient with Lyme disease Tezzon F.*, Corradini C.**, Huber R.**, Egarter Vigl E.***, Simeoni J:****, Stanek G.*****, Ferrari G.* * Divisione di Neurologia, Ospedale Civile Maggiore, Verona ** Divisione di Neurologia, Ospedale di Bolzano *** Divisione di Patologia, Ospedale di Botzano **** Divisione di lgiene, Ospedale di Bolzano ***** Hygiene Institute, University of Vienna
Lyme borreliosis is an infectious disease caused by the spirochete Borrelia burgdorferi. Neurological complications are frequently reported but the pathogenesis remains largely unknown. We report on a patient with positive borrelia antibodies at ELISA and immunoblotting and with histological and immunofluorescence study of peripheral nerve biopsy consistent with vasculitic neuropathy.
Key-Words: Lyme disease -- neuroborreliosis - - vasculitis - - vasculitic mononeuritis multiplex
Introduction Lyme borreliosis is an infectious disease caused by the spirochete Borrelia burgdorferi which is transmitted by ticks of the genus Ixodes [13] and other hematoperagous arthropods. This infectious disease may be either of short duration and without consequences or severe, chronic and disabling. A characteristic early symptom is the annular skin lesion erythema chronicum migrans (ECM), related to the region of the bite [15]. It may be followed by neurological [ 11] and/or cardiac abnormalities several weeks to months later [13], or by arthritis weeks or even years later. Neurological, heart and joint manifestation are not necessarily preceded by ECM. Neurological manifestations are extremely variable, including cranial mono-multineuritis, aseptic meningitis, encephalitis and encephalomyelitis, transverse myelitis, polyradiculoneuropathies and mononeuritis multiplex as single entities or in various combinations [6]. Received 20 April 1990 - Accepted 30 August 1990
We report on a patients with positive Borrelia antibodies at ELISA and immunoblotting and with histological and immunofluorescence findings on peripheral nerve biopsy specimen consistent with vasculitic neuropathy. Case report A 63 year old woman was admitted to our department on October '88 because of weakness of the legs and of the left hand with painful paresthesias in the regions of the left ulnar nerve, right sural nerve and both peroneal nerves. Five months before (June, 1988) she complained of a painful red lesion on the left leg that expanded and paled inthe centre. She suffered from headache, general malaise and fatigue. The lesion and the concomitant subjective symptoms resolved within a few weeks without special medical treatment. The patient could not recall any "insect" bite. Two months after the appearance of the erythematous reaction (September, 1988), numbness and pain229
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ful tingling appeared over the dorsum of the left foot with weakness of the tibialis anterior and extensor hallueis longus muscles. During the following weeks she noticed a painful sensation on the ulnar side of the left hand and weakness of the intrinsic left hand muscles. On admission to our department, sensory disturbances involving the right tibial nerve and weakness of the right calf muscles were also evident. Family history revealed no hereditary neurological disorder. There was no occupational exposure to toxic agents and no history of diabetes mellitus, liver, kidney or rheumatic disease. She lived in an alpine village in the South Tyrol, an area endemic for Borrelia infections [I 2]. Her mental status was normal. Cranial nerves were also normal. Manual muscle testing revealed a marked loss of strenght of the intrinsic muscles in the left hand and of the left peroneal and right calf muscles. Left ulnar jerk as well as both ankle jerks were absent. Touch and pain sensation were reduced at the ulnar side of the left hand, over the dorsum of both feet and on the right sole and heel. There was no tremor.
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Laboratory findings Normal or negative laboratory values included electrolytes, calcium, phosphorus, blood glucose, blood urea nitrogen, liver enzymes, urinalysis, B~2and folate, thyroid function tests, venereal disease laboratory (VDRL) test, acid phosphatase. Red and white blood cell counts were normal. The Westgren erythrocyte sedimentation rate was 56 m m / h r (normal < 15). Routine serum protein electrophoresis and quantitative analysis of serum immunoglobulins were in the normal range. Antinuclear antibodies (ANA), latex rheumatoid factor as well as cryogiobulins were absent. Complement C3 fraction was very low and circulating immune complexes determined by Cl-q binding were elevated. CSF examination showed normal cell count and glucose content, but a mild increase in the protein content (54 mg/di; normal: < 45 mg/dl), normal lgG index and no oligoclonal bands [9]. Borrelia ELISA and immunoblotting were performed as described elsewhere [13, 14]. The serum was positive but not the CSF (Fig. 1).
Electrophysiological findings Electromyography of the left tibialis anterior and extensor digitorum brevis muscles showed fibrillation potentials and positive sharp waves with marked reduction of recruitment of motor unit potentials on voluntary effort. No compound 230
Fig. !. lmmunobloting o f serum and CSF to sonicated Borrelia burgdorferi. No positivity was found with the CSF. motor response could be evoked from the extensor digitorum brevis after stimulation of the left peroneal nerve. Fibrillation potentials and positive sharp waves were evident also in the fight tibialis anterior and gastrocnemius muscles. The ulnar sensory response was absent. Sensory conduction velocity of the left sural nerve was normal; no potential could be elicited from the right surai nerve.
Nerve biopsy study Paraffin section of the left superficial peroneal nerve biopsy study showed lymphocytic and mononuclear cell infiltration of epineural arterioles with fibrinoid necrosis and thickening of the tunica media of the vessel wall (Fig. 2). Semithin transverse epoxy sections showed marked loss of myelinated and unmyelinated fibers. Teased fiber analysis showed myelin ovoids, consistent with wallerian degeneration. Direct immunofluorescence of frozen sections of the nerve with antisera coupled with fluorescein isothiocyanate (Fig. 3) showed transmural deposition of lgG, IgA and complement (C3) [10].
Tezzon E: Vasculitic mononeuritis multiplex in Lyme disease
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Fig. 2. Transverse paraffin section of superficiale peroneal nerve; epineural blood vessel showing intense transmural inflammatory cell infiltration, fibrinoid necrosis and virtual disappearance of the lumen. Part of a nerve fascicle is shown (N). Hematoxylin and eosin, original magnification x 25O
Fig. 3. Direct immunofluorescence reaction for C3 with antisera coupled with fluorescein isothiocyanate. A single epineurial vessel is shown with transmural granular deposits. Identical patterns were found with antisera to IgG, lgA and fibrinogen.
Discussion
but no evidence of medial vasonecrosis was found; further, immunofluorescence studies proved normal. Our biopsy findings were consistent with vasculitis of epineurial arterioles and with ischemic wallerian degeneration of nerve fibers [5]. Moreover, our immunofluorescence finding supported the postulate of an immune complex pathogenic mechanism similar to what is seen in serum sickness and immune complex disease. Nevertheless, the unambiguous conclusion that immune complex deposits initiated the immunological process is not possibile and immunoglobulins with complement could have been trapped in the cell-infiltrated blood vessel wall. Both processes -- immune complex deposition and primary inflammatory cell infiltration - - might have resulted in the final vascular damage of peripheral nerves. In our experience treatment with corticosteroids (prednisone 25 mg/die for two months) after ceftriaxone at the recommended dosage (2 g/die for 14 days) [3] was followed by clinical improvement and no relapse was observed, thereafter.
On the basis of clinical, EMG, serological and pathological findings, the diagnosis ofmononeuritis multiplex associated with a Borrelia burgdorferi infection was made. In Lyme borreliosis the most common neurological feature is meningopolyneuritis [2, 11, 17]. Nevertheless, it is remarkable that any of the many neurological manifestations may occur alone - - e.g. mononeuritis multiplex --. In our ease no meningitic or encephalitic symptoms were evident and CSF examination showed only a moderately increased protein concentration with minimal damage of the brain-blood barrier. Similar pattern have been reported only occasionally and may present diagnostic difficulties [1, 8, 11]. The pathogenesis of mononeuritis multiplex is still not established: Pachner and Steere [11 ] say that vasculitis is probably responsible. In their series of 10 patients Vallat et al. [17] showed infiltrations of lymphocytes and plasma cells around epineural, peri- and endoneurial vessels
Sommario
La borreliosi di Lyme b una malattia infettiva causata dalla spirochete Borrelia burgdo~feri. Le complicanze neuroiogiche sono segnalate con frequenza, ma la loro patogenesi rimane oscura. Noi presentiamo il caso di un paziente con positivitiz di anticorpi al test ELISA e con studio istologico e di immunofluorescenza di una biopsia del nervo periferico che comprova l'esistenza di una neuropatia vasculitica. 231
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Address reprint requests to Dr. Frediano Tezzon Divisione di Neurologia Ospedale Borgo Trento 37126 Verona
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