CASE REPORT Lyme cerebral vasculitis
The Enlarging Clinical Spectrum of Lyme Disease: Lyme Cerebral Vasculitis, a New Disease Entity The case of a patient with cerebral vasculitis with a right thalamic infarct associated with cerebral spinal fluid Lyme disease is presented. This entity has not been described in the United States, and only one similar case in the wqrld literature could be found. The patient presented with a progressive headache and subsequent development of grand real seizure activity. Lyme disease has been associated with cranial nerve palsies, peripheral and cranial radiculopathies, aseptic meningitis, encephalitic symptoms, chorea, and demyeiinating polyneuropathy presenting like Guillain-Barr~ syndrome. These syndromes can occur separately or in combination. Stroke and strokelike syndromes have been attributed to Lyme disease. The literature concerning the neurologic manifestations of Lyme disease is reviewed. [Brogan GX, Homan CS, Viecellio P: The enlarging clinical spectrum of Lyme disease: Lyme cerebral vasculitis, a new disease entity. Ann Emerg Med May 1990;19:572-576.] INTRODUCTION The diagnosis of Lyme disease can be very difficult. The case of a 37year-old woman who presented with new onset of headache syndrome and seizure activity associated with positive cerebral spinal fluid (CSF) Lyme antibody titers is described. Only one case of similar etiology was found in the world literatureJ
Gerard X Brogan, MD Clark S Homan, MD Peter Viccellio, MD Stony Brook, New York From the School of Medicine, SUNY/Stony Brook, Stony Brook, New York. Received for publication September 13, 1989. Revision received December 1, 1989. Accepted for publication December 21, 1989. Address for reprints: Gerard X Brogan, MD, Program in Emergency Medicine, School of Medicine, University Hospital, L4, 515, SUNY/Stony Brook, Stony Brook, New York 11794-7400.
CASE REPORT A 37-year-old woman presented to the emergency department complaining of a severe headache. The pain had started 24 hours earlier, was associated with tearing, and was relieved with acetaminophen. The headache recurred five hours before presentation. The patient described the pain as the worst headache of her life. The pain started behind the left eye and progressed to a severe bandlike pulsating pain across the forehead. There was associated nausea but no vomiting, aura, fever, visual changes, salivation, rhinorrhea, or tearing. Family history was negative for vascular headaches, and there was no history of trauma. The patient was ten days postpartum after a cesarean section and had a history of hypothyroidism treated with levothyroxine sodium. The pregnancy was complicated by in vitro fertilization and premature labor at 30 wee~s' gestation treated by tocolysis with ritodrine. The vital signs were unlemarkable. The patient was not hypertensive and was afebrile. Her funduscopic examination was within normal limits without hemorrhage or papilledema, and meningismus was not present. The remainder of the physical examination, including a nonfocal neurologic examination, was nnremarkable. Initial laboratory results were hematocrit, 38.4%; hemoglobin, 1Z.9 g%; and WBC, 15.7 x 103 with 85 segments, two bands, eight lymphocytes, and five monocytes. The electrolytes, BUN, and creatinine were within normal limits. The urinalysis showed 6 to 8 WBCs/high-power field and 2 to 3 RBCs/high-power field with moderate epithelial cells and few bacteria. An erythrocyte sedimentation rates was normal. She was sent for a noncontrast computed tomography (CT) scan of the head, which was negative. At this time, the headache intensified, and the patient was noted to have left ptosis and flattening of the left nasolabial
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LYME DISEASE Brogan, Homan & Viccellio
FIGURE 1. CT scan of head w i t h contrast showing acute infarct in right thalamic region near the posterior limb of the ir2ternal capsule. fold associated with nausea. She was alert, pupils were equal and reactive, and the extraocular movements were intact. The patient could contract the upper face, and there was no associated hemiparesis. A lumbar puncture was performed. While the CSF analysis was pending, the patient developed a grand real seizure that was treated with diazepam and phenytoin. The patient returned to the CT scan suite for repeat head scans with and without contrast. The contrast scan revealed an acute nonhemorrhagic infarct in the right thalamic region near the posterior limb of the internal capsule (Figure 1). The CSF results available at this time were significant for 178 mg/dL protein, 40 RBC/mm 3, 1 WBC/mm 3, and a negative Gram stain. The VDRL, cryptococcal antigen, tuberculosis, and fungal tests performed on the CSF were negative. The patient was admitted to the ICU. A cerebral angiogram performed the next day revealed irregular smallto-moderate-sized vessels with narrowing and beading in the frontal and parietal regions. The left side had greater involvement than the right. The venous phase of the angiogram ruled out the possibility of venous sinus thrombosis. This reading was consistent with vasculitis (Figure 2). The EEG revealed paroxysmal slowing with no lateralizing features. The laboratory workup for systemic vasculitis or hypercoagulable state was negative;-this included a normal erythrocyte sedimentation rate, fibrinogen, antinuclear antibody, C-reactive protein, urine immunoelectrophoresis, s e r u m i m m u n o electrophoresis, rheumatoid factor, total serum c o m p l e m e n t , antithrombin III, protein S, rapid plasma reagin test, complement component C3, c o m p l e m e n t c o m p o n e n t C4, anti-rho, and anti-la. Aortography was not performed. The patient was treated initially with prednisone for cerebral vasculitis, with slight i m p r o v e m e n t . Two days after hospitalization, the serum and CSF serology studies were completed and revealed positive antibody titers for Lyme disease in both serum and CSF. The serum Lyme ti124/573
ter was 0.200 by optical density measurement with a control of 0.091, and the CSF Lyme titer was 0.167 by optical density measurement With a control of 0.091. The steroid therapy was discontinued. Treatment with 2 g ceftriaxone 1V each day was instituted, resulting in resolution of symptoms. Follow-up angiography two months later showed a significant decrease in the amount of irregularity, beading, and narrowing compared with the initial examination (Figure 3).
DISCUSSION Lyme disease is typically a tickAnnals of Emergency Medicine
borne infection that may involve the central nervous system. The spirochete Borrelia burgdorferi is the causative organism. ~ Lyme disease is the most frequently reported tickborne disease; it is most common in the northeastern United States but has been documented nationwide,3, 4 in Canada, s and worldwide. 6 Ixodes d a m m i n i is the tick that has been identified as largely responsible for the spread of the disease. 7 However, s t u d i e s have d e m o n s t r a t e d t h a t horseflies, mosquitos, and deerflies can also become infected. 8 There is one documented case of human infection secondary to a bite from a fly19:5 May 1990
FIGURE 2. Internal carotid angiogram demonstrating segmental narrowing irregularities and beading of small and moderate size vessels with relative dilation in the segments distal to the narrowing.
ing arthropod.9 Studies have been performed showing that the disease can be passed by contact transmission without a tick as the vector.m, 11 Often, the disease begins with a characteristic skin rash, erythema chronicum migrans, and generalized symptoms such as fever, headache, and arthralgia, which is referred to as stage 1.12,13 Stage 2 occurs w h e n other organs such as the central nervous system, joints, and heart become involved, usually several weeks to months later.12,14 If effective therapy is not administered, the disease may progress to the chronic stage 3. Manifestations of this stage may include acrodermatitis chronica atrophicans, chronic oligoarthritis, and progressive e n c e p h a l o m y e l i tis. 15,16 However, the clinical syndrome does not always manifest itself according to this staging system, as observed in patients at our institution. Cardiac involvement is believed to occur in 8% of patients with Lyme disease. 13 Neurologic involvement occurs in 11%, and arthritis develops in 40%. 16 Often, Lyme disease will present without a history of tick bite or antecedent rash; one study described several cases of advanced central nervous system Lyme disease 19:5 May 1990
that lacked this history. 17 Our case is interesting from the perspective of the initial clinical presentation in the ED because there were no specific contributing elements from the history regarding tick bite or occupational exposure as risks for Lyme disease. There was no history of a rash resembling erythema chronicum migrans. Also, initially there were no previous neurologic, cardiac, or arthritic manifestations. Institutions such as ours that are located in a c o m m u n i t y where Lyme disease is considered endemic frequently include Lyme disease in the differential of patients with a variety of neurologic complaints. Neurologic abnormalities are seen in 11% to 15% of B burgdorferi infections. The broad s p e c t r u m of neurologic symptoms secondary to Lyme disease makes the presentation highly variable. The literature has identified many different entities that may occur separately or together, Is i n c l u d i n g c r a n i a l neuropathies, radiculopathies, aseptic meningitis, encephalitic symptoms, demyelinating polyneuropathy, mononeuritis multiplex, and pseudotumor cerebri. 19 The clinical presentation of cerebral vasculitis typically includes one Annals of Emergency Medicine
or m o r e central n e r v o u s s y s t e m symptoms, such as headache, alteration of consciousness, seizures, or focal signs. Visual signs may be present in approximately 35% of patients. The erythrocyte sedimentation rate is typically normal, and the blood leukocyte count may be normal or elevated. The CSF may show an elevated leukocyte count and typically demonstrates an elevated protein, as in our patient. Focal ischemic lesions as well as hemorrhages may be seen on head CT scanning. The beaded appearance of the central nervous system vessels with areas of narrowing and irregularity are the classic findings on cerebral angiography. ~o Confirmation of the diagnosis of central nervous system Lyme disease is made by the presence of elevated titers of serum and CSF antibodies specific for B burgdorferi. 19 There is a subset of patients who may have positive CSF titers and negative serum levels. Typical CSF findings are increased protein and immunoglobulins and a lymphocyte and monocyte pleocytosis. 21 As recently described, a seronegative patient with signs and symptoms consistent with Lyme disease probably should have an analysis of specific T-celt blastogenic response to B burgdorferi before Lyme disease is excluded. 22 Our case illustrates a new mechan i s m by w h i c h the Borrelia spirochete can involve the central nervous system. The pathophysiology of the vasculitis is not adequately understood. One postulated mechanism of the central nervous system vasculitis implicates the IgM cryoglobulins as causative factors. 16,23-~5 In the other case reported in the world literature, the patient had an elevated serum and CSF IgM antibody titer to B burgdorferi before treatment; three months after therapy, the titers were both negative. Findings similar to those of our patient have been observed in meningovascular syphilis and noninfectious arteritis.22, 26 It is not clear whether the vascular changes observed are a result of invasion of the CSF by the Borrelia organ574/125
LYME DISEASE Brogan, Homan & Viccellio
FIGURE 3. Follow-up angiogram two months later showing significant decrease in the amount of irregularity, beading, and narrowing compared with initial study, ism or caused by i m m u n e mechanisms without the local presence of the infectious agent, such as in imm u n e - c o m p l e x - m e d i a t e d disease. The recognition of such complexes in patients with postinfectious diseases and central nervous system vasculitis suggests that the antigenic features of these organisms stimulate formation of antigen-antibody complexes that induce damage to the vascular endothelium. 27 As our case report suggests, Lyme disease must be included in the differential of any pat i e n t p r e s e n t i n g w i t h signs and symptoms consistent with cerebral vasculitis, particularly patients with geographic risk factors. Other causes of intracranial vasculitis include hypersensitivity vasculitis, polyarteritis nodosa, Wegener's granulomatosis, lymphomatoid granulomatosis, giant cell arteritis, and Behchet's disease. Other infectious causes, such as syphilis, can also be responsible. One of the more common manifestations of central nervous s y s t e m Lyme disease is Bell's palsy. Involvement of the fifth cranial nerve can be unilateral or bilateral and may occur s i m u l t a n e o u s l y or weeks apart. 28 The third, fourth, sixth, and eighth cranial nerves have also been involved. Presentations may vary and include extraocular movement alteration, papilledema, optic atrophy, otalgia, dizziness, and sore throat. Aseptic meningitis is usually insidious in onset and may start with recurrences of stiff neck, headache, nausea, vomiting, and photophobia. The CSF often shows a pleocytosis or lymphocytosis, and the IgG usually is increased. The opening pressure may be normal or increased. The patient may have a single episode or develop a chronic form. a9 Lymphocytic meningoradiculitis, which occurs in Europe and is called Bannwath's syndrome, is now believed to be caused by B burgdorferi, go E n c e p h a l i t i s m a y o c c u r in any form. Presentation may range from lethargy and fatigue to psychoses, dementia, and seizures. 31 Radiculopathies resembling those of herpes zoster also have been de126/575
scribed. Similar to Bell's palsy, involvement may be unilateral or bilateral and simultaneous or occur at different times. Motor involvement may be greater than sensory involvement. The m o s t c o m m o n dermatomes involved are cranial nerves V, C-5, and T8-12.~o,24 Other manifestations of Lyme disease i n c l u d e c h o r e a g2 and pseud o t u m o r cerebri~ 16 Guillain-Barr4 syndrome has also been described, g3 Therapy for early Lyme disease is oral penicillin, tetracycline, amoxicillin-clavulanic acid, or amoxicillin with or without probenecid. Treatment for the later stages of the disease changes because there is greater difficulty in obtaining effective therapy. IV penicillin G 20 million units/ day IV has been widely used for stage 3 Lyme disease. 34 Also, studies perf o r m e d by D a t t w y l e r et al have s h o w n ceftriaxone to be effective against resistant Lyme disease. 3s In fact, r e c e n t studies suggest that ceftriaxone is more effective than high-dose penicillin therapy, g6 T h r o u g h o u t this d i s c u s s i o n of Lyme disease, many similarities between Lyme disease and syphilis become evident. In particular, our patient displayed a cerebral vasculitis with similarities to that caused by syphilis. C o m m o n features of the Annals of Emergency Medicine
two entities include spirochetes as causative agent, early skin manifestations, stages of clinical disease, prevalence of living spirochetes in tissues for many years, chronic disease involving the central nervous system, and effective treatment with antibiotics.
SUMMARY Lyme serologies should be ordered when signs or symptoms consistent with central nervous system Lyme disease are recognized, as in our patient, who presented in an area where Lyme disease is endemic. Although the complaint of headache is common in the clinical presentation of Lyme disease, one must be aware of the various pathophysiologic mechanisms that may produce headache symptoms in this disease. A cerebral angiogram may be indicated in a subset of patients to elucidate the pathophysiology responsible for the particular presentation. As Lyme disease becomes more prevalent, this entity must be in a physician's differential diagnosis when patients present with central n e r v o u s s y s t e m , r h e u m a tologic, or cardiac signs or symptoms without an obvious etiology. The authors express their thanks to Connie Meade and JoAnn Broumay for their 19:5 May 1990
assistance in preparing this m a n u s c r i p t .
12. Col F, Bruhn W: Lyme disease. A m J Dis Child 1984;138:467-470.
25. Pachner AR: Spirochetal diseases of the CNS. Neurol Clin 1986;4:207-222.
REFERENCES
13. Steere AC, Batsford WP, Weinberg M, et ah Lyme carditis: Cardiac abnormalities of Lyme disease. Ann Intern Med 1980;93:8-16.
26. Aldrich MS, Burke JM, Gulati 8M: Angiographic findings in a young man with recurrent stroke and positive fluorescent treponemal antibody. Stro/.e 1983;14:1001-1004.
1. Uldry PA, Regli F, Bogousslavsky J: Cerebral angiopathy and recurrent strokes following Borrelia burgdorferd infection: J Neurol Neurosurg Psychiatry. 1987;50:1703-1704.
14. Meyerhoff J: Lyme disease. A m J Med 1983;75:663-670.
2. Steere AC, Grodzicki RL, Kornblatt AN, et al: The spirocheta] etiology of Lyme disease. N Engl J Med 1983;308:733-740.
15. Reik L, Smith L, Kahn A, et ah Demyelinating encephalopathy in Lyme disease. Neurology 1985;35:267-269.
3. Taylor RD, Harris MP: Lyme disease: A case report from South Carolina. J SC Med Assoc 1985;81:419-420.
16. Reik L, Steere AC, Bartenhagen NH, et ah Neurologic abnormalities of Lyme disease. Medicine 1979;51h281-294.
4. Davis JP, Schell WL, Amundson TE; et al: Lyme disease in Wisconsin: Epidemiologic clinical, serologic, and entomologic findings. Yale J Biol Med 1984;57:685-696. 5. Lycka BASi Lyme disease in Canada? Can Med Assoc J 1986;134:d8-49. 6. Schmid GP: The global distribution of Lyme disease. Rev Infect Dis 1985;7:41-50. 7. Steere AC, Malawista SE: Cases of Lyme disease in the United States: Locations correlated with distribution Ixodes dammini. Ann Intern Med 1979;91:730-733. 8. Magnarelli LA, Anderson JF, Barbour AG: The etiologic agent of Lyme disease in deer flies, horse flies, and mosquitoes. J Inf Dis 1986;154:355-358. 9. Guandolo VL: Atypical Lyme disease or forme fruste. Md Med J 1985;34:687-692. 10. Burgess EC: Experimental infection of dogs with Borrelia burgdorferi. Int J Microbiol Hyg 1986;263:49-54. 11. Burgess EC, Amundson TA, Davis J, et ah Experimental innoculation of Peromyscus species with Borrelia burgdorferi: Evidence of contact transmission. A m J Trop Med Hyg 1986; 35: 359-363.
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17. Reik L, Burgdorfer W, Donaldson J: Neurologic abnormalities in Lyme disease without erythema chronicum migrans. A m J Med 1986; 81:73-78. 18. Pachner AR, Steere AC: The triad of neurologic manifestations of Lyme disease: Meningitis, craninal neuritis and radiculoneuritis. Neurology 1985;35:47-53. 19. Finkel M: Lyme disease and its neurologic complications. Arch Neurol 1988;45:99-104. 20. Launes J, Iivanainen M, Erkinjuntti T, et ah Isolated angitis of the central nervous system. Acta Neurol Scand 1986;74:108-114. 21. Weder B, Weidersheim P, Matter L, et ah Chronic progressive neurological involvement in Borrelia burgdorferi infection. J Neurol 1987; 234:40-43. 22. Dattwyler RJ, Volkmen DJ, Luft BJ, et ah 8eronegative Lyme disease. N Engl J Med 1988; 319:1441-1446. 23. 8tiernstedt G: Tick-borne Borrelia infection in Sweden. Scand J Infect Dis 1985;45:1-70. 24. Pachner AR, Steere AC: Neurological findings of Lyme disease. Yale [ Biol Med 1984;57: 481-483.
Annals of Emergency Medicine
27. Reik L: Disseminated vasculomyelinepathy: An immune complex disease. Ann Neurol 1980;7:291-296. 28. Schmutzhard E, Stanek G: Borrelia burgdorferi: A possible cause of Bell's palsy? Clin Neurol Neurosurg 1985;87:255-257. 29. Skoldenberg B, Stiernstedt G, Garde A, et al: Chronic meningitis caused by a penicillinsensitive organism? Lancet 1983;2:75-78. 30. Kovanen J, Schauman K, Valkas J: Bannwarth's syndrome and Lyme disease in Finland. 8cand J Infect Dis 1986;18:421-424. 31. Kohler J, Kasper J, Kern U, et ah Borrelia encephalomyelitis. Lancet 1986;2:35. 32. Goldfarb J, Williams CL, Jacobson RI, et ah Neurological complications of Lyme disease in children {abstract). Twenty-fifth Interscience Conference on Antimicrobial Agents and Chemotherapy, 1985, abstract 386. 33. Sterman AB, Nelson S, Barclay P: Demyelinating neuropathy accompanying Lyme disease. Neurology 1982; 32:1302-1305. 34. Steere AC, Pachner AR, Malawista S: Successful treatment of the neurologic abnormalities of Lyn ~ disease with high-dose intravenous penicillin. Ann Intern Med 1983~99: 767-772. 35. Dattwyler RJ, Halperin JJ, Pass H, et ah Ceftriaxone as effective therapy in refractory Lyme disease. J Infect Dis 1987;155:1322-1325. 36. Luft B, Volkman D, Halperin J, et al: New chemotherapeutic approaches in the treatment of Lyme Borreliosis. Ann N Y Acad Sci 1988; 539:352-361.
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The Enlarging Clinical Spectrum of Lyme Disease: Lyme Cerebral Vasculitis, a New Disease Entity The case of a patient with cerebral vasculitis with a right thalamic infarct associated with cerebral spinal fluid Lyme disease is presented. This entity has not been described in the United States, and only one similar case in the wqrld literature could be found. The patient presented with a progressive headache and subsequent development of grand real seizure activity. Lyme disease has been associated with cranial nerve palsies, peripheral and cranial radiculopathies, aseptic meningitis, encephalitic symptoms, chorea, and demyeiinating polyneuropathy presenting like Guillain-Barr~ syndrome. These syndromes can occur separately or in combination. Stroke and strokelike syndromes have been attributed to Lyme disease. The literature concerning the neurologic manifestations of Lyme disease is reviewed. [Brogan GX, Homan CS, Viecellio P: The enlarging clinical spectrum of Lyme disease: Lyme cerebral vasculitis, a new disease entity. Ann Emerg Med May 1990;19:572-576.] INTRODUCTION The diagnosis of Lyme disease can be very difficult. The case of a 37year-old woman who presented with new onset of headache syndrome and seizure activity associated with positive cerebral spinal fluid (CSF) Lyme antibody titers is described. Only one case of similar etiology was found in the world literatureJ
Gerard X Brogan, MD Clark S Homan, MD Peter Viccellio, MD Stony Brook, New York From the School of Medicine, SUNY/Stony Brook, Stony Brook, New York. Received for publication September 13, 1989. Revision received December 1, 1989. Accepted for publication December 21, 1989. Address for reprints: Gerard X Brogan, MD, Program in Emergency Medicine, School of Medicine, University Hospital, L4, 515, SUNY/Stony Brook, Stony Brook, New York 11794-7400.
CASE REPORT A 37-year-old woman presented to the emergency department complaining of a severe headache. The pain had started 24 hours earlier, was associated with tearing, and was relieved with acetaminophen. The headache recurred five hours before presentation. The patient described the pain as the worst headache of her life. The pain started behind the left eye and progressed to a severe bandlike pulsating pain across the forehead. There was associated nausea but no vomiting, aura, fever, visual changes, salivation, rhinorrhea, or tearing. Family history was negative for vascular headaches, and there was no history of trauma. The patient was ten days postpartum after a cesarean section and had a history of hypothyroidism treated with levothyroxine sodium. The pregnancy was complicated by in vitro fertilization and premature labor at 30 wee~s' gestation treated by tocolysis with ritodrine. The vital signs were unlemarkable. The patient was not hypertensive and was afebrile. Her funduscopic examination was within normal limits without hemorrhage or papilledema, and meningismus was not present. The remainder of the physical examination, including a nonfocal neurologic examination, was nnremarkable. Initial laboratory results were hematocrit, 38.4%; hemoglobin, 1Z.9 g%; and WBC, 15.7 x 103 with 85 segments, two bands, eight lymphocytes, and five monocytes. The electrolytes, BUN, and creatinine were within normal limits. The urinalysis showed 6 to 8 WBCs/high-power field and 2 to 3 RBCs/high-power field with moderate epithelial cells and few bacteria. An erythrocyte sedimentation rates was normal. She was sent for a noncontrast computed tomography (CT) scan of the head, which was negative. At this time, the headache intensified, and the patient was noted to have left ptosis and flattening of the left nasolabial
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LYME DISEASE Brogan, Homan & Viccellio
FIGURE 1. CT scan of head w i t h contrast showing acute infarct in right thalamic region near the posterior limb of the ir2ternal capsule. fold associated with nausea. She was alert, pupils were equal and reactive, and the extraocular movements were intact. The patient could contract the upper face, and there was no associated hemiparesis. A lumbar puncture was performed. While the CSF analysis was pending, the patient developed a grand real seizure that was treated with diazepam and phenytoin. The patient returned to the CT scan suite for repeat head scans with and without contrast. The contrast scan revealed an acute nonhemorrhagic infarct in the right thalamic region near the posterior limb of the internal capsule (Figure 1). The CSF results available at this time were significant for 178 mg/dL protein, 40 RBC/mm 3, 1 WBC/mm 3, and a negative Gram stain. The VDRL, cryptococcal antigen, tuberculosis, and fungal tests performed on the CSF were negative. The patient was admitted to the ICU. A cerebral angiogram performed the next day revealed irregular smallto-moderate-sized vessels with narrowing and beading in the frontal and parietal regions. The left side had greater involvement than the right. The venous phase of the angiogram ruled out the possibility of venous sinus thrombosis. This reading was consistent with vasculitis (Figure 2). The EEG revealed paroxysmal slowing with no lateralizing features. The laboratory workup for systemic vasculitis or hypercoagulable state was negative;-this included a normal erythrocyte sedimentation rate, fibrinogen, antinuclear antibody, C-reactive protein, urine immunoelectrophoresis, s e r u m i m m u n o electrophoresis, rheumatoid factor, total serum c o m p l e m e n t , antithrombin III, protein S, rapid plasma reagin test, complement component C3, c o m p l e m e n t c o m p o n e n t C4, anti-rho, and anti-la. Aortography was not performed. The patient was treated initially with prednisone for cerebral vasculitis, with slight i m p r o v e m e n t . Two days after hospitalization, the serum and CSF serology studies were completed and revealed positive antibody titers for Lyme disease in both serum and CSF. The serum Lyme ti124/573
ter was 0.200 by optical density measurement with a control of 0.091, and the CSF Lyme titer was 0.167 by optical density measurement With a control of 0.091. The steroid therapy was discontinued. Treatment with 2 g ceftriaxone 1V each day was instituted, resulting in resolution of symptoms. Follow-up angiography two months later showed a significant decrease in the amount of irregularity, beading, and narrowing compared with the initial examination (Figure 3).
DISCUSSION Lyme disease is typically a tickAnnals of Emergency Medicine
borne infection that may involve the central nervous system. The spirochete Borrelia burgdorferi is the causative organism. ~ Lyme disease is the most frequently reported tickborne disease; it is most common in the northeastern United States but has been documented nationwide,3, 4 in Canada, s and worldwide. 6 Ixodes d a m m i n i is the tick that has been identified as largely responsible for the spread of the disease. 7 However, s t u d i e s have d e m o n s t r a t e d t h a t horseflies, mosquitos, and deerflies can also become infected. 8 There is one documented case of human infection secondary to a bite from a fly19:5 May 1990
FIGURE 2. Internal carotid angiogram demonstrating segmental narrowing irregularities and beading of small and moderate size vessels with relative dilation in the segments distal to the narrowing.
ing arthropod.9 Studies have been performed showing that the disease can be passed by contact transmission without a tick as the vector.m, 11 Often, the disease begins with a characteristic skin rash, erythema chronicum migrans, and generalized symptoms such as fever, headache, and arthralgia, which is referred to as stage 1.12,13 Stage 2 occurs w h e n other organs such as the central nervous system, joints, and heart become involved, usually several weeks to months later.12,14 If effective therapy is not administered, the disease may progress to the chronic stage 3. Manifestations of this stage may include acrodermatitis chronica atrophicans, chronic oligoarthritis, and progressive e n c e p h a l o m y e l i tis. 15,16 However, the clinical syndrome does not always manifest itself according to this staging system, as observed in patients at our institution. Cardiac involvement is believed to occur in 8% of patients with Lyme disease. 13 Neurologic involvement occurs in 11%, and arthritis develops in 40%. 16 Often, Lyme disease will present without a history of tick bite or antecedent rash; one study described several cases of advanced central nervous system Lyme disease 19:5 May 1990
that lacked this history. 17 Our case is interesting from the perspective of the initial clinical presentation in the ED because there were no specific contributing elements from the history regarding tick bite or occupational exposure as risks for Lyme disease. There was no history of a rash resembling erythema chronicum migrans. Also, initially there were no previous neurologic, cardiac, or arthritic manifestations. Institutions such as ours that are located in a c o m m u n i t y where Lyme disease is considered endemic frequently include Lyme disease in the differential of patients with a variety of neurologic complaints. Neurologic abnormalities are seen in 11% to 15% of B burgdorferi infections. The broad s p e c t r u m of neurologic symptoms secondary to Lyme disease makes the presentation highly variable. The literature has identified many different entities that may occur separately or together, Is i n c l u d i n g c r a n i a l neuropathies, radiculopathies, aseptic meningitis, encephalitic symptoms, demyelinating polyneuropathy, mononeuritis multiplex, and pseudotumor cerebri. 19 The clinical presentation of cerebral vasculitis typically includes one Annals of Emergency Medicine
or m o r e central n e r v o u s s y s t e m symptoms, such as headache, alteration of consciousness, seizures, or focal signs. Visual signs may be present in approximately 35% of patients. The erythrocyte sedimentation rate is typically normal, and the blood leukocyte count may be normal or elevated. The CSF may show an elevated leukocyte count and typically demonstrates an elevated protein, as in our patient. Focal ischemic lesions as well as hemorrhages may be seen on head CT scanning. The beaded appearance of the central nervous system vessels with areas of narrowing and irregularity are the classic findings on cerebral angiography. ~o Confirmation of the diagnosis of central nervous system Lyme disease is made by the presence of elevated titers of serum and CSF antibodies specific for B burgdorferi. 19 There is a subset of patients who may have positive CSF titers and negative serum levels. Typical CSF findings are increased protein and immunoglobulins and a lymphocyte and monocyte pleocytosis. 21 As recently described, a seronegative patient with signs and symptoms consistent with Lyme disease probably should have an analysis of specific T-celt blastogenic response to B burgdorferi before Lyme disease is excluded. 22 Our case illustrates a new mechan i s m by w h i c h the Borrelia spirochete can involve the central nervous system. The pathophysiology of the vasculitis is not adequately understood. One postulated mechanism of the central nervous system vasculitis implicates the IgM cryoglobulins as causative factors. 16,23-~5 In the other case reported in the world literature, the patient had an elevated serum and CSF IgM antibody titer to B burgdorferi before treatment; three months after therapy, the titers were both negative. Findings similar to those of our patient have been observed in meningovascular syphilis and noninfectious arteritis.22, 26 It is not clear whether the vascular changes observed are a result of invasion of the CSF by the Borrelia organ574/125
LYME DISEASE Brogan, Homan & Viccellio
FIGURE 3. Follow-up angiogram two months later showing significant decrease in the amount of irregularity, beading, and narrowing compared with initial study, ism or caused by i m m u n e mechanisms without the local presence of the infectious agent, such as in imm u n e - c o m p l e x - m e d i a t e d disease. The recognition of such complexes in patients with postinfectious diseases and central nervous system vasculitis suggests that the antigenic features of these organisms stimulate formation of antigen-antibody complexes that induce damage to the vascular endothelium. 27 As our case report suggests, Lyme disease must be included in the differential of any pat i e n t p r e s e n t i n g w i t h signs and symptoms consistent with cerebral vasculitis, particularly patients with geographic risk factors. Other causes of intracranial vasculitis include hypersensitivity vasculitis, polyarteritis nodosa, Wegener's granulomatosis, lymphomatoid granulomatosis, giant cell arteritis, and Behchet's disease. Other infectious causes, such as syphilis, can also be responsible. One of the more common manifestations of central nervous s y s t e m Lyme disease is Bell's palsy. Involvement of the fifth cranial nerve can be unilateral or bilateral and may occur s i m u l t a n e o u s l y or weeks apart. 28 The third, fourth, sixth, and eighth cranial nerves have also been involved. Presentations may vary and include extraocular movement alteration, papilledema, optic atrophy, otalgia, dizziness, and sore throat. Aseptic meningitis is usually insidious in onset and may start with recurrences of stiff neck, headache, nausea, vomiting, and photophobia. The CSF often shows a pleocytosis or lymphocytosis, and the IgG usually is increased. The opening pressure may be normal or increased. The patient may have a single episode or develop a chronic form. a9 Lymphocytic meningoradiculitis, which occurs in Europe and is called Bannwath's syndrome, is now believed to be caused by B burgdorferi, go E n c e p h a l i t i s m a y o c c u r in any form. Presentation may range from lethargy and fatigue to psychoses, dementia, and seizures. 31 Radiculopathies resembling those of herpes zoster also have been de126/575
scribed. Similar to Bell's palsy, involvement may be unilateral or bilateral and simultaneous or occur at different times. Motor involvement may be greater than sensory involvement. The m o s t c o m m o n dermatomes involved are cranial nerves V, C-5, and T8-12.~o,24 Other manifestations of Lyme disease i n c l u d e c h o r e a g2 and pseud o t u m o r cerebri~ 16 Guillain-Barr4 syndrome has also been described, g3 Therapy for early Lyme disease is oral penicillin, tetracycline, amoxicillin-clavulanic acid, or amoxicillin with or without probenecid. Treatment for the later stages of the disease changes because there is greater difficulty in obtaining effective therapy. IV penicillin G 20 million units/ day IV has been widely used for stage 3 Lyme disease. 34 Also, studies perf o r m e d by D a t t w y l e r et al have s h o w n ceftriaxone to be effective against resistant Lyme disease. 3s In fact, r e c e n t studies suggest that ceftriaxone is more effective than high-dose penicillin therapy, g6 T h r o u g h o u t this d i s c u s s i o n of Lyme disease, many similarities between Lyme disease and syphilis become evident. In particular, our patient displayed a cerebral vasculitis with similarities to that caused by syphilis. C o m m o n features of the Annals of Emergency Medicine
two entities include spirochetes as causative agent, early skin manifestations, stages of clinical disease, prevalence of living spirochetes in tissues for many years, chronic disease involving the central nervous system, and effective treatment with antibiotics.
SUMMARY Lyme serologies should be ordered when signs or symptoms consistent with central nervous system Lyme disease are recognized, as in our patient, who presented in an area where Lyme disease is endemic. Although the complaint of headache is common in the clinical presentation of Lyme disease, one must be aware of the various pathophysiologic mechanisms that may produce headache symptoms in this disease. A cerebral angiogram may be indicated in a subset of patients to elucidate the pathophysiology responsible for the particular presentation. As Lyme disease becomes more prevalent, this entity must be in a physician's differential diagnosis when patients present with central n e r v o u s s y s t e m , r h e u m a tologic, or cardiac signs or symptoms without an obvious etiology. The authors express their thanks to Connie Meade and JoAnn Broumay for their 19:5 May 1990
assistance in preparing this m a n u s c r i p t .
12. Col F, Bruhn W: Lyme disease. A m J Dis Child 1984;138:467-470.
25. Pachner AR: Spirochetal diseases of the CNS. Neurol Clin 1986;4:207-222.
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