we cannot document the number of angiomas present. However, the pathological specimens and the long clinical course are evidence against a neoplastic or infectious cause. This patient's symptoms were due to documented increased intracranial pressure. Evidence for intracranial o r subarachnoid hemorrhage was not present, nor was communicating hydrocephalus likely because ventricular size o n CAT scan was normal. Perhaps an abnormal blood-brain barrier is associated with these lesions, resulting in multiple areas of increased extracellular fluid and cerebral edema and thus the pseudotumorlike presentation. The association in this patient of multiple cryptic vascular malformations of the nervous system and increased intracranial pressure with normal ventricular size is unique. Without computerized tomographic evaluation, the lesions would have been missed, In addition, the association of increased pressure with multiple foci of edema is atypical for patients with vascular malformations. T h e patient's beneficial response to the CSF shunting increases the importance of recognizing this disease entity.
Bell's Palsy and Secondary Syphilis: CSF Spirochetes Detected by Immunofluorescence Larry E. Davis, MD, and Sally Sperry, MT (ASCP) ~~
We are grateful to Dr William McCormick for his review of thc pathology. We also wish to acknowledge the assistance of Drs Kenneth Maravello, Bassett Kilgore, and Hal McCready with the CAT scans, and the cooperation of Drs Dale Schulz, Michael Burt, and David Josephson of Methodist Hospital, Indianapolis, IN.
References HP, Subbiah B, Bosch EP: Neurologic aspects of hereditary hemorrhagic telangiectasia. Arch Neurol 34: 101104, 1977 2. Boczko M L Neurological implications of hereditary hemorrhagic telangectasis. J Nerv Ment Dis 139:525-536, 1964 3. Craig WM, Wagener HP, Kernohan J W Lindau-von Hipprl disease-a report of four cases. Arch Neurol Psychiatry 4636-54, 1941 4. Kleinhirncysteni B: Pathogenese und Beziehungen zur Angiomatosis retinae. Arvid Lindav Suppl 1, 1926 5 . McCormick WF: The pathology of vascular (arteriovenous) malformation. J Neurosurg 24807-816, 1966 6. McCormick WF, Nofzinger JD: Cryptic vascular malformations of the central nervous system. J Neurosurg 249634375, 1966 7. Michael JC, Levin PM: Multiple telangiectases of the brain. Arch Neurol 36:514-529, 1936 8. Noran HH: lntracranial vascular tumors and malformations. Arch Pathol 39393-416, 1945 9. Osler W: Case of- asthma with cyanosis, extensive purpura, painful muscles and eosinophilia. Johns Hopkins Hosp Bull 12:17, 1901 10. Rubinstein LJ: Tumors of the central nervous system, in Atlas of Tumor Pathology. Washington, DC, Armed Forces Institute of Pathology, 1972, fasc 6, pp 245-246 11. Russell DS: Pathology of spontaneous intracranial hemorrhage. Proc R SOCMed 47:689-693, 1954 12. Russell DS, Rubinstein LJ: Pathology of Tumors of the Nervous System. Baltimore, Williams & Wilkins, 1971, p p 93-98 1. Adams
378
~
~~
~~
Although Bell's palsy is usually idiopathic, occasional cases may have an identifiable infectious cause. When facial paralysis results from syphilis, it usually develops during the tertiary meningovascular stage. We report a 30-year-old man with secondary syphilis who developed facial paralysis associated with acute syphilitic meningitis. Spirochetes were identified in the cerebrospinal fluid by immunofluorescence using standard reagents from the fluorescent treponemal antibody absorption (FTA-ABS) test. Patients with Bell's palsy should be screened for syphilis with a blood FTA-ABS test, and treatment with corticosteroids should be considered only after an infectious cause has been excluded. Davis LE, Sperry S: Bell's palsy and secondary syphilis: CSF spirochetes detected by immunofluorescence. Ann Neurol4:378-380, 1978 Bell's palsy is usually a benign disorder without identifiable cause. Occasionally, however, the facial paralysis has recognizable causes, including infections. Park and Watkins [8] found an infectious origin in 6% of 500 cases. Tuberculous meningitis, leprosy, varicella zoster, rubella, mumps, Epstein-Barr virus, syphilis, and bacterial infections of the middle ear have all been associated with facial paralysis [l]. Although meningovascular syphilis is recognized as a cause of palsies of the cranial nerve, including the facial nerve [6], secondary syphilis rarely leads to Bell's palsy. Merritt and Moore [7] reviewed a large series of patients with syphilis and identified only 2 with secondary syphilis who developed isolated facial nerve palsy from acute syphilitic meningitis. This report describes another patient who developed Bell's palsy during secondary syphilis. Spirochetes were identified in the patient's cerebrospinal fluid by immunofluorescent study. From the Departments of Neurology and Pathology, University of New Mexico School of Medicine, and the Veterans Administration Hospital, Albuquerque, NM. Accepted for publication Mar 22, 1978. Address reprint requests to Dr Davis, Department of Neurology, University of New Mexico School of Medicine, Albuquerque, N M 87131.
0364-5134/78/0004-0415$01.00 @ 1978 by Larry E. Davis
A 30-year-old man developed a mild headache lasting several days, followed by acute right facial weakness. A physician noted right facial paresis and a maculopapular erythematous rash involving the trunk and extremities, including the palms. Bell's palsy was diagnosed, and the patient was treated with 60 m g of prednisone per day for two weeks. The rash disappeared but the facial weakness progressed. The headaches continued, and mild, high-pitched tinnitus developed. Six weeks later the patient saw another physician. Examination disclosed right peripheral facial paralysis, diminished taste sensation o n the right side of the tongue, anterior and posterior cervical lymphadenopathy, and moderate patchy alopecia. Function of the other cranial nerves was normal except for a bilateral high-tone hearing loss, confirmed by audiometry. T h e remainder of the physical examination was normal. T h e patient gave no history of a primary syphilitic lesion and said that one year previously he had had a negative blood test for syphilis. The CSF had an opening pressure of 170 m m H,O with 0 red blood cells, and 125 white cells per cubic millimeter (80% lymphocytes); 53 m d d l glucose; 106 rngldl protein, of which 22%) was gamma globulin; and sterile bacterial, tuberculosis, and fungal cultures. The CSF Venereal Disease Research Laboratory (CSF-VDRL) test was reactive when assayed undiluted, and the CSF fluorescent treponemal antibody absorption (CSF-FTA-ABS) test was 1 reactive. T h e serum rapid plasma reagin test was reactive at 1:128 dilution, and a fluorescent treponemal antibody absorption (FTA-ABS) test was strongly reactive. The patient was treated with penicillin €or three weeks. After one month, movement of the right face returned and the headaches, tinnitus, and adenopathy were gone. Examination of the CSF after treatment showed 5 lymphocytes/mm3, 48 m d d l protein, a nonreactive VDRL test, and a borderlinereactive CSF-FTA-ABS test.
+
Special CSF Stadies Two milliliters each of frozen CSF obtained at admission and following treatment were thawed and centrifuged at 18,000 rpm for 30 minutes. Each pellet was smeared o n two clean glass microscopic slides, air dried, and fixed in acetone for 10 minutes. T h e reagents and methods of staining in this study were those used in the FTA-ABS test for blood syphilis serology [ 1 I]. One slide prepared from each CSF sample and a third prepared with FTA-ABS antigen (Lederle Diagnostics, Pearl River, NY) were stained with specific syphilis antiserum. O n e slide prepared from the initial CSF sample and a second FTA-ABS antigen slide were stained with FTA-ABS nonsyphilitic serum to serve as controls.
Results I n the admission CSF sediment stained with FTAABS reactive serum, 15 complete spirochetes having the size and configuration of Treponema pallidurn were identified by dark-field microscopy. These spirochetes also showed specific fluorescence when examined under ultraviolet light (Figure). The intensity of the fluorescent staining was the same as for the control FTA-ABS antigen stained with FTA-ABS
Fluorescent antibody staining of CSF Spirochete by FTA-ABS reactice antireram ( x 1,000).
reactive serum. O n the admission CSF sediment slide stained with FTA-ABS nonsyphilitic serum, no fluorescent spirochetes or spirochete fragments were identified. The FTA-ABS nonsyphilitic serum did not stain the control FTA-ABS antigen. No spirochetes were identified by dark-field or fluorescent microscopy in the posttreatment CSF sediment. Discussion The diagnosis of secondary syphilis was based on typical signs and a reactive FTA-ABS test. Acute syphilitic meningitis was present, with spirochetes demonstrated in the CSF by immunofluorescence. Spirochetes have only rarely been identified in the CSF of patients with secondary or tertiary syphilis in spite of the presumption that they are there 12, 31. Since T . pallidum will currently grow only in animals, routine bacterial cultures are sterile [9]. Identification of spirochetes from fresh specimens is difficult under light-field microscopy and usually requires dark-field examination [9]. However, CSF is seldom examined by dark-field microscopy. Once T . pallidum has become nonmotile, identification becomes even more difficult since cell debris may simulate a spirochete. Immunofluorescent microscopy has been used successfully to identify fixed, nonmotile T . pallidum spirochetes in smears made from primary syphilitic skin lesions [ 5 ] . A similar approach was used to identify the nonmotile spirochetes in the CSF of this patient. Because the reagents used are from the FTA-ABS test, the capability of searching for T . pallidurn spirochetes in CSF or in lesions elsewhere already exists in many hospital laboratories. Although no fluorescent spirochetes were seen in the admission CSF sediment stained with nonsyphilitic serum, some caution must be exercised in the interpretation of that finding. Rabbits infected with T . pallidurn have been shown to develop antibody that will intrinsically coat its organisms, resulting in
Case Report: Davis and Sperry: Bell's Palsy and Syphilis 379
spirochetes that fluoresce when stained only with fluorescein-conjugated antirabbit IgG [ 121. This may also occur in man. T o best exclude the possibility of intrinsic antibody coating, a portion of the sample should also be stained with fluorescein conjugated antihuman globulin alone. Whether administration of corticosteroids contributed to worsening of the facial paresis in this patient remains speculative. Animals experimentally infected with syphilis had greater numbers of spirochetes and showed a more aggressive spread of tbe disease when steroids were given [4, 101. Corticosteroids for the treatment of Bell's palsy should be considered, if at all, only after infectious causes have been excluded. Supported by the Research Service of the Veterans Administration. The authors thank Mrs B. Mitchell and Drs S. Johnson, D. Seelinger, and K. Tung for their help with this study.
References 1. Brackman DE: Bell's palsy. Incidence, etiology, and results of medical treatment. Otolaryngol Clin North Am ?:35?-368, 1974
380 Annals of Neurology Vol 4 No 4 October 1978
2. Chesney AM, Kemp JE: Incidence of Spirochaeta pallida in cerebrospinal fluid during early stage of syphilis. JAMA 83:1?25-1728, 1924 3. Collart P, Franceschini P, Poitevin M, e t al: Modified method of filtering cerebrospinal fluid and aqueous humour for the detection of treponemes. Br J Vener Dis 50:251-256, 1974 4. DeLameter ED, Saureno V, Urbach F: Studies on immunology of spirochetoses. 1 . Effect of cortisone o n spirochetes. Am J Syph 36:127-139, 1952 5 . Edwards EA: Detecting Treponerna pallidurn in primary lesions by the fluorescent antibody technique. Pub1 Health Rep 77:427-430, 1962 6 . Gilroy J, Meyer JS: Medical Neurology. SecoLd edition. New York, Macmillan, 1975, pp 393-404 7 . Merritt HH, Moore M: Acute syphilitic meningitis. Medicine 14:119-183, 1935 8. Park H W , Watkins AL: Facial paralysis. Analysis of 500 cases. Arch Phys Med 30:749-761, 1949 9. Smith DT: Treponema pallidurn and syphilis, in Joklik WK, Smith DT (eds): Zinsser Microbiology. 15th edition. New York, Appleton-Century-Crofts, 1972, pp 642-650 10. Turner TB, Hollander DH: Cortisone in experimental syphilis. Johns Hopkins Hosp Bull 87:505-509, 1950 1 1 . Venereal Disease Research Laboratory: Manual of Tests for Syphilis--1969 (Public Health Service publication no. 41 1 ) . Washington, DC, US Government Printing Office, 1969, pp 15-22 12. Wilkinson AE, Rayner CFA: Studies on the fluorescent treponemal antibody (FTA) test. Br J Vener Dis 42%-14, 1966
Bell's Palsy and Secondary Syphilis: CSF Spirochetes Detected by Immunofluorescence Larry E. Davis, MD, and Sally Sperry, MT (ASCP) ~~
We are grateful to Dr William McCormick for his review of thc pathology. We also wish to acknowledge the assistance of Drs Kenneth Maravello, Bassett Kilgore, and Hal McCready with the CAT scans, and the cooperation of Drs Dale Schulz, Michael Burt, and David Josephson of Methodist Hospital, Indianapolis, IN.
References HP, Subbiah B, Bosch EP: Neurologic aspects of hereditary hemorrhagic telangiectasia. Arch Neurol 34: 101104, 1977 2. Boczko M L Neurological implications of hereditary hemorrhagic telangectasis. J Nerv Ment Dis 139:525-536, 1964 3. Craig WM, Wagener HP, Kernohan J W Lindau-von Hipprl disease-a report of four cases. Arch Neurol Psychiatry 4636-54, 1941 4. Kleinhirncysteni B: Pathogenese und Beziehungen zur Angiomatosis retinae. Arvid Lindav Suppl 1, 1926 5 . McCormick WF: The pathology of vascular (arteriovenous) malformation. J Neurosurg 24807-816, 1966 6. McCormick WF, Nofzinger JD: Cryptic vascular malformations of the central nervous system. J Neurosurg 249634375, 1966 7. Michael JC, Levin PM: Multiple telangiectases of the brain. Arch Neurol 36:514-529, 1936 8. Noran HH: lntracranial vascular tumors and malformations. Arch Pathol 39393-416, 1945 9. Osler W: Case of- asthma with cyanosis, extensive purpura, painful muscles and eosinophilia. Johns Hopkins Hosp Bull 12:17, 1901 10. Rubinstein LJ: Tumors of the central nervous system, in Atlas of Tumor Pathology. Washington, DC, Armed Forces Institute of Pathology, 1972, fasc 6, pp 245-246 11. Russell DS: Pathology of spontaneous intracranial hemorrhage. Proc R SOCMed 47:689-693, 1954 12. Russell DS, Rubinstein LJ: Pathology of Tumors of the Nervous System. Baltimore, Williams & Wilkins, 1971, p p 93-98 1. Adams
378
~
~~
~~
Although Bell's palsy is usually idiopathic, occasional cases may have an identifiable infectious cause. When facial paralysis results from syphilis, it usually develops during the tertiary meningovascular stage. We report a 30-year-old man with secondary syphilis who developed facial paralysis associated with acute syphilitic meningitis. Spirochetes were identified in the cerebrospinal fluid by immunofluorescence using standard reagents from the fluorescent treponemal antibody absorption (FTA-ABS) test. Patients with Bell's palsy should be screened for syphilis with a blood FTA-ABS test, and treatment with corticosteroids should be considered only after an infectious cause has been excluded. Davis LE, Sperry S: Bell's palsy and secondary syphilis: CSF spirochetes detected by immunofluorescence. Ann Neurol4:378-380, 1978 Bell's palsy is usually a benign disorder without identifiable cause. Occasionally, however, the facial paralysis has recognizable causes, including infections. Park and Watkins [8] found an infectious origin in 6% of 500 cases. Tuberculous meningitis, leprosy, varicella zoster, rubella, mumps, Epstein-Barr virus, syphilis, and bacterial infections of the middle ear have all been associated with facial paralysis [l]. Although meningovascular syphilis is recognized as a cause of palsies of the cranial nerve, including the facial nerve [6], secondary syphilis rarely leads to Bell's palsy. Merritt and Moore [7] reviewed a large series of patients with syphilis and identified only 2 with secondary syphilis who developed isolated facial nerve palsy from acute syphilitic meningitis. This report describes another patient who developed Bell's palsy during secondary syphilis. Spirochetes were identified in the patient's cerebrospinal fluid by immunofluorescent study. From the Departments of Neurology and Pathology, University of New Mexico School of Medicine, and the Veterans Administration Hospital, Albuquerque, NM. Accepted for publication Mar 22, 1978. Address reprint requests to Dr Davis, Department of Neurology, University of New Mexico School of Medicine, Albuquerque, N M 87131.
0364-5134/78/0004-0415$01.00 @ 1978 by Larry E. Davis
A 30-year-old man developed a mild headache lasting several days, followed by acute right facial weakness. A physician noted right facial paresis and a maculopapular erythematous rash involving the trunk and extremities, including the palms. Bell's palsy was diagnosed, and the patient was treated with 60 m g of prednisone per day for two weeks. The rash disappeared but the facial weakness progressed. The headaches continued, and mild, high-pitched tinnitus developed. Six weeks later the patient saw another physician. Examination disclosed right peripheral facial paralysis, diminished taste sensation o n the right side of the tongue, anterior and posterior cervical lymphadenopathy, and moderate patchy alopecia. Function of the other cranial nerves was normal except for a bilateral high-tone hearing loss, confirmed by audiometry. T h e remainder of the physical examination was normal. T h e patient gave no history of a primary syphilitic lesion and said that one year previously he had had a negative blood test for syphilis. The CSF had an opening pressure of 170 m m H,O with 0 red blood cells, and 125 white cells per cubic millimeter (80% lymphocytes); 53 m d d l glucose; 106 rngldl protein, of which 22%) was gamma globulin; and sterile bacterial, tuberculosis, and fungal cultures. The CSF Venereal Disease Research Laboratory (CSF-VDRL) test was reactive when assayed undiluted, and the CSF fluorescent treponemal antibody absorption (CSF-FTA-ABS) test was 1 reactive. T h e serum rapid plasma reagin test was reactive at 1:128 dilution, and a fluorescent treponemal antibody absorption (FTA-ABS) test was strongly reactive. The patient was treated with penicillin €or three weeks. After one month, movement of the right face returned and the headaches, tinnitus, and adenopathy were gone. Examination of the CSF after treatment showed 5 lymphocytes/mm3, 48 m d d l protein, a nonreactive VDRL test, and a borderlinereactive CSF-FTA-ABS test.
+
Special CSF Stadies Two milliliters each of frozen CSF obtained at admission and following treatment were thawed and centrifuged at 18,000 rpm for 30 minutes. Each pellet was smeared o n two clean glass microscopic slides, air dried, and fixed in acetone for 10 minutes. T h e reagents and methods of staining in this study were those used in the FTA-ABS test for blood syphilis serology [ 1 I]. One slide prepared from each CSF sample and a third prepared with FTA-ABS antigen (Lederle Diagnostics, Pearl River, NY) were stained with specific syphilis antiserum. O n e slide prepared from the initial CSF sample and a second FTA-ABS antigen slide were stained with FTA-ABS nonsyphilitic serum to serve as controls.
Results I n the admission CSF sediment stained with FTAABS reactive serum, 15 complete spirochetes having the size and configuration of Treponema pallidurn were identified by dark-field microscopy. These spirochetes also showed specific fluorescence when examined under ultraviolet light (Figure). The intensity of the fluorescent staining was the same as for the control FTA-ABS antigen stained with FTA-ABS
Fluorescent antibody staining of CSF Spirochete by FTA-ABS reactice antireram ( x 1,000).
reactive serum. O n the admission CSF sediment slide stained with FTA-ABS nonsyphilitic serum, no fluorescent spirochetes or spirochete fragments were identified. The FTA-ABS nonsyphilitic serum did not stain the control FTA-ABS antigen. No spirochetes were identified by dark-field or fluorescent microscopy in the posttreatment CSF sediment. Discussion The diagnosis of secondary syphilis was based on typical signs and a reactive FTA-ABS test. Acute syphilitic meningitis was present, with spirochetes demonstrated in the CSF by immunofluorescence. Spirochetes have only rarely been identified in the CSF of patients with secondary or tertiary syphilis in spite of the presumption that they are there 12, 31. Since T . pallidum will currently grow only in animals, routine bacterial cultures are sterile [9]. Identification of spirochetes from fresh specimens is difficult under light-field microscopy and usually requires dark-field examination [9]. However, CSF is seldom examined by dark-field microscopy. Once T . pallidum has become nonmotile, identification becomes even more difficult since cell debris may simulate a spirochete. Immunofluorescent microscopy has been used successfully to identify fixed, nonmotile T . pallidum spirochetes in smears made from primary syphilitic skin lesions [ 5 ] . A similar approach was used to identify the nonmotile spirochetes in the CSF of this patient. Because the reagents used are from the FTA-ABS test, the capability of searching for T . pallidurn spirochetes in CSF or in lesions elsewhere already exists in many hospital laboratories. Although no fluorescent spirochetes were seen in the admission CSF sediment stained with nonsyphilitic serum, some caution must be exercised in the interpretation of that finding. Rabbits infected with T . pallidurn have been shown to develop antibody that will intrinsically coat its organisms, resulting in
Case Report: Davis and Sperry: Bell's Palsy and Syphilis 379
spirochetes that fluoresce when stained only with fluorescein-conjugated antirabbit IgG [ 121. This may also occur in man. T o best exclude the possibility of intrinsic antibody coating, a portion of the sample should also be stained with fluorescein conjugated antihuman globulin alone. Whether administration of corticosteroids contributed to worsening of the facial paresis in this patient remains speculative. Animals experimentally infected with syphilis had greater numbers of spirochetes and showed a more aggressive spread of tbe disease when steroids were given [4, 101. Corticosteroids for the treatment of Bell's palsy should be considered, if at all, only after infectious causes have been excluded. Supported by the Research Service of the Veterans Administration. The authors thank Mrs B. Mitchell and Drs S. Johnson, D. Seelinger, and K. Tung for their help with this study.
References 1. Brackman DE: Bell's palsy. Incidence, etiology, and results of medical treatment. Otolaryngol Clin North Am ?:35?-368, 1974
380 Annals of Neurology Vol 4 No 4 October 1978
2. Chesney AM, Kemp JE: Incidence of Spirochaeta pallida in cerebrospinal fluid during early stage of syphilis. JAMA 83:1?25-1728, 1924 3. Collart P, Franceschini P, Poitevin M, e t al: Modified method of filtering cerebrospinal fluid and aqueous humour for the detection of treponemes. Br J Vener Dis 50:251-256, 1974 4. DeLameter ED, Saureno V, Urbach F: Studies on immunology of spirochetoses. 1 . Effect of cortisone o n spirochetes. Am J Syph 36:127-139, 1952 5 . Edwards EA: Detecting Treponerna pallidurn in primary lesions by the fluorescent antibody technique. Pub1 Health Rep 77:427-430, 1962 6 . Gilroy J, Meyer JS: Medical Neurology. SecoLd edition. New York, Macmillan, 1975, pp 393-404 7 . Merritt HH, Moore M: Acute syphilitic meningitis. Medicine 14:119-183, 1935 8. Park H W , Watkins AL: Facial paralysis. Analysis of 500 cases. Arch Phys Med 30:749-761, 1949 9. Smith DT: Treponema pallidurn and syphilis, in Joklik WK, Smith DT (eds): Zinsser Microbiology. 15th edition. New York, Appleton-Century-Crofts, 1972, pp 642-650 10. Turner TB, Hollander DH: Cortisone in experimental syphilis. Johns Hopkins Hosp Bull 87:505-509, 1950 1 1 . Venereal Disease Research Laboratory: Manual of Tests for Syphilis--1969 (Public Health Service publication no. 41 1 ) . Washington, DC, US Government Printing Office, 1969, pp 15-22 12. Wilkinson AE, Rayner CFA: Studies on the fluorescent treponemal antibody (FTA) test. Br J Vener Dis 42%-14, 1966
