Journal of
J. Neurol. 219, 199--204 (1978) t~) by Springer-Vedag 1978
Cochleovestibular Involvement as the First Sign of Syphilis J. P. Hungerbfihler and F. Regli Service de Neurologie du Centre hospitalier universitaire vaudois, CH-1011 Lausanne, Switzerland
Summary. Three cases of syphilis with cochleovestibular symptoms are reported. There was either cochlear or vestibular involvement in two cases and, in the third, cochlear and vestibular involvement together. The disorder was unilateral in all three. In one case ~there was a concurrent lesion of the oculomotor nerve which was the motive for consultation. There was no other s y m p t o m suggesting the diagnosis of syphilis in any case. The important features of diagnosis are discussed. Key words: Neurosyphilis - Cranial nerve lesions - Cochlear disorder Vestibular disorder.
Zusammenfassung.Es werden drei Fiille einer cochleo-vestibul~iren luetischen Erkrankung geschildert. Je einmal war lediglich die cochle~ire bzw. die vestibul~ire Funktion betroffen, w~ihrend im dritten Fall beide Funktionen beeintr~ichtigt waren. Die L~ision war immer einseitig. In einem Fall war noch der N. okulomotorius betroffen. Es waren keine anderen klinischen Zeichen der luetischen Affektion nachweisbar. Die diagnostischen, therapeutischen und pathogenetischen Aspekte dieser luetischen Komplikation werden am Schlul3 diskutiert.
Introduction We recently had the opportunity to observe three cases of neurosyphilis presenting initially with cochleovestibular symptoms, without a prior history of, or other symptoms suggesting syphilis. Our purpose is to remind the physician of the existence of such an etiology for cochleovestibular symptoms, which, even if rare, can be encountered in that isolated ~brm. Indeed, in view of the frequency of vascular, toxic, non-specific inflammator 3, auricular affections and of the general impression of a decline in the number of cases of syphilis, as well as a certain lack of interest in syphilis itself, and the changing pattern of syphilis, the syphilitic nature of an auricular affection may actually be missed by the physician in the absence of any other suggestive sign.
0340-5354/78/0219/0199/$ 01.20
200
J.P. Hungerbiihler and E Regti
Case Reports Case 1 A man aged 40 was in good health until July 1975, when nausea, vomiting, dizziness and gait disturbance occurred and forced him to stay in bed. One day later the symptoms disappeared, A few weeks later the same attack recurred lasting for the same period of time. In November 1975, he began to complain of diplopia on right lateral gaze and downward.
lnitial Examination (November 1975) revealed a man in generally good condition. On neurological examination there was incomplete paralysis of the left inferior oblique muscle but no hearing loss, or nystagmus. The gait showed a tendency to deviate to the right with closed eyes and there was some unsteadiness on Romberg test. The rest of the examination was normal. Otological examinatior~ revealed the effects of otitis media and vestibular dysfunction but no hearing loss.
"Laboratory Findings. Routine laboratory data, EEG, Doppler examination of the carotids, gammaencephalography and cisternography (isotopic) were all normal. Examination of the CSF revealed clear cerebrospinal fluid, 42/3 leucocytes with 55% lymphocytes and 45% moncytes, glucose 11 mg%, protein 48 rag% and non-specific inflammatory reaction on protein electrophoresis. Research of sarcoidosis was negative.
Syphilis Reactions. Blood: Kolmer and VDRL positive 1/~,Nelson and FTA-ABS tests positive:
CSF: Kolmer and VDRL negative, FTA-ABS test positive. Subsequent Course. The patient received penicillin therapy (exact description see below). Within the following months the diplopia disappeared, there was no relapse of dizziness and the levels of Kolmer and VDRL decreased.
Case 2 A patient of 46 years was in good health until the abrupt appearance of tinnitus in the left ear with progressive deafness on the same side occurring within a few hours.
lnitial Examination (March 1976) revealed a patient in good general condition. Neurological examination disclosed only decreased hearing in the left ear with the Rinne test positive bilaterally and the Weber test lateralized to the right, Otological examination revealed a bearing loss of 70 db at 8 000 HZ (perception type) in the left ear and no vestibular dysfunction.
Laboratory Findings. Routine laboratory data were normal. Examination of the CSF revealed clear cerebrospinal fluid, 6/3 leucocytes with 46% lymphocytes, 24% monocytes, 4% polynuclear cells, 26% lymphoplasmocytes, protein 32mg%, glucose 59mg% and on protein electrophoresis there was a slight elevation of gammaglobulins with elevation of IgG and IgM present.
Syphilitic Reactions. Blood: Kolmer and VDRL were positive (~), Nelson and FTA-ABS tests positive; CSF: Kolmer and VDRL negative, FTA-ABS test positive.
Subsequent Course. The patient received a course of penicillin. The hearing loss remained unchanged while the tinnitus disappeared. The levels of Kolmer and VDRL are decreasing.
Case 3 A patient aged 50, whose medical history included a cerebral concussion at the age of 20 and moderate hypertension known for several months, began to feel abnormally tired on 11 October 1976 and experienced nausea and vomiting; he also had a gait disturbance and clumsiness of the left hand.
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lnitial Physical Examination (December 1976) was within normal limits but on neurological examination, there was horizontal and rotatory nystagmus on right lateral gaze, a tendency to deviate to the left when upright and on Unterberger test, no apparent hearing loss and a discreet diminution of vibratory sense in the legs. Audiometric studies revealed a hearing loss of 50 db (perception type) in the left ear and vestibular examination disclosed dysfunction on the left side with caloric hyporeflexia and normal rotatory response. Laboratory Findings. Routine laboratory data were all normal. Rhumatoid, latex test, australian antigen, LE cells and antinuclear antibody were negative. Neurological laboratory data were also normal except for the CFS results: clear cerebrospinal fluid, 26/3 leucocytes with 51% lymphocytes, 41% monocytes, 7% plasma cells, 485/3 red cells, glucose 58 mg%, protein 65 mg%, abnormal normomastix, and on protein electrophoresis elevation of gammaglobulins, with IgG 15.6 mg% (N = 2 to 4 mg%), IgM 6.85 mg% (N = 0) on immunoelectrophoresis. Syphilitic Reactions. Blood: Kolmer and VDRL positive (~64), Nelson and FTA-ABS positive; CSF: Kolmer and VDRL positive (~4), Nelson and FTA-ABS positive. Subsequent Course. The patient received a course of penicillin. Within the following months the symptoms disappeared and his neurological status returned to normal (according to his physician). The level of Kolmer and VDRL has been decreasing. Treatment in each case consisted of penicillin therapy 2.4 Mo Penicillin G IM Penadur LA twice during 4 weeks after corticotherapy has been given for a few days in order to prevent a Herxheimer reaction. Regular Control of VDRL and Kolmer with examination of CSF have been programmed.
Comments The three p a t i e n t s s h o w e d features c o r r e s p o n d i n g to the classical d e s c r i p t i o n o f the i n v o l v e m e n t o f the eight nerve in syphilis [1, 12--14, 16--22, 26--28]. The first p a t i e n t h a d a r e c u r r e n t unilateral vestibular d i s o r d e r c h a r a c t e r i z e d b y vertigo, nausea, unsteadiness a n d a t e n d e n c y to deviate to the right. The second p a t i e n t h a d unilateral c o c h l e a r i n v o l v e m e n t with r a p i d l y progressing hearing loss. The t h i r d h a d features o f c o c h l e a r a n d vestibular lesions: nausea, vomiting, unsteadiness, t e n d e n c y to deviate to the left a n d on o t o l o g i c a l e x a m i n a t i o n h e a r i n g loss o f the p e r c e p t i o n type as well as dissociated vestibular p e r i p h e r a l d y s f u n c t i o n on the left side. As can easily be stated, there are not e n o u g h characteristic features in this s y m p t o m a t o l o g y to orient the diagnosis t o w a r d a syphilitic etiology. I n d e e d the i n v o l v e m e n t o f the eighth cranial nerve with syphilis presents no characteristic elements, consisting either o f dissociated d i s o r d e r (cochlear or vestibular) o r a s s o c i a t e d c o c h l e a r a n d v e s t i b u l a r involvement, which m a y be either unilateral o r b i l a t e r a l o c c u r r i n g a b r u p t l y or in a progressive way. The course m a y be r e m i t t e n t so that, if c o c h l e a r a n d vestibular involvement occur t o g e t h e r it is difficult to distinguish the d i s o r d e r f r o m Meni~re's disease. Sparse s y m p t o m a t o l o g y a n d s p o n t a n e o u s cures have also been r e p o r t e d . A m o n g features which can suggest the diagnosis is the occurrence o f such s y m p t o m s in a p a t i e n t often still y o u n g in otherwise g o o d c o n d i t i o n . H o w e v e r , this e t i o l o g y m u s t be distinguished f r o m o t h e r diseases such as viral d i s o r d e r s which are m u c h m o r e frequent, even in y o u n g people. The difficulty a n d the interesting fact in the three patients was the occurrence o f these s y m p t o m s w i t h o u t c o n c u r r e n t o r p r i o r signs o f syphilis. A n e x p l a n a t i o n
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of such an evolution could be the unawareness of the affection by the patient or the reluctance to confess it. Yet our patients denied having noticed prior symptoms, even after the diagnosis had been made known to them. Therefore we consider this symptomatology represents the true evolution of the three cases without other indications of syphilis, even if we cannot be absolutely certain. Such a course has been described several times [17, 19, 20, 22] and with or without prior signs of syphilis, the cochleovestibular involvement can be the first sign of neurosyphilis. This.involvement occurs most frequently in the first 18 months of the infection but can be encountered in the late stages [17]. Interesting too is the fact that the eighth cranial nerve is one of the most frequently involved beside the second, third, and seventh cranial nerves [17]. Not rarely the lesion of the eighth cranial nerve occurs with involvement of another cranial nerve (the most frequently involved are the seventh and the third) either simultaneously or successively, also suggesting the diagnosis; so our third patient had an oculomotor involvement which was the motive for consultation. The nature of the lesion of the eighth nerve [17, 19--22] is generally thought to be a neurolabyrinthitis which may involve either the nerve or the labyrinth. As mentioned above, this involvement may occur in different stages of the disease: in secondary, tertiary and tabetic stages as well as with congenital syphilis. In the secondary stage this neurolabyrinthitis seems to be a meningoneuritis localized to the sheath of the auricular nerve in association with vascular lesions, secondarly to the penetration of the treponema pallidum in the leptomeningeal space. There may be simultaneous involvement of other cranial nerves. In the tertiary stage, in addition to the meningoneuritis, primary inflammatory parenchymatous lesions affecting the labyrinth, the labyrinthine paths of their centers (polioencephalitis) and lesions secondary to the extension of middle ear involvement (otolabyrinthitis) have been proposed. Polioencephalitis arising from the meningoneuritis and denervative nervous lesions have been postulated in the tabetic stage. Some authors have also described a labyrinthine periostitis. In view of the pleocytosis and the involvement of another cranial nerve we think the first patient had a meningoneuritis. In the second patient the absence of pleocytosis and the isolated cochlear involvement could suggest a primary parenchymatous inflammatory lesion of the labyrinth. In the third patient, the CSF pleocytosis, the cochleovestibular involvement and the syphilitic tests all positive, in the absence of clinical signs of the tabetic stage, suggest a meningoneuritis, although another type of lesion is not ruled out. Regarding the clinical stage of the affection, it is extremely difficult to conclude, in the absence of any other sign of the disease. However, the most probable seems to be a secondary or tertiary stage in all our patients although, particularly in the third patient the beginning of tabes cannot be entirely excluded. Indeed a lesion of the eighth nerve may also be the first sign of tabes, even if it is probably extremely rare in such an isolated form. As stated above, the diagnosis of syphilis in these cases depends on serological tests and the CSF examination [2, 3, 23--25]. With our patients all syphilitic tests were positive in the blood. Yet, in CSF, if FTA-ABS test were all positive, V D R L and Kolmer were positive only once (Case 3). We think the negative result of these two tests in the CSF does not exclude the diagnosis in presence of a positive F T A -
Cochleovestibular Involvement as the First Sign of Syphilis
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ABS test, for the FTA-ABS test appears to be the most sensitive and specific test attesting the penetration o f treponema pallidum in the CSF (9) with the very rare false positive results, usually with a type of affection practically excluded in these cases; on the other hand dissociated reactions particularly in the CSF have been described in proven cases of neurosyphilis [10, 19, 20, 33, 15]. The absence of the usual CSF pleocytosis in the second patient is still compatible with the diagnosis, especially if an isolated labyrinthine lesion is postulated, in the presence of a positive FTA-ABS test in the CSF. The unusual hypoglycorachia (I 1 rag%) in our first patient led us to search for several diseases which could have given such a result. But after other possible diagnoses were excluded, the positive results of the syphilitic tests and the favourable evolution after treatment are indicative of a syphilitic origin. However, in the first two cases in particular we cannot completely rule out the occurrence of two diseases, namely a latent neurosyphilis and another neurological involvement resolving spontaneously, although it seems unlikely. What is the frequency of such an evolution? It is not easy to answer this question. Even now public health data are incomplete, often based on partial or false information. Fleming and Brown estimated in two studies [5, 9] that 80% of cases of syphilis were treated by private physicians and only a quarter to a third of all cases were reported to the health authorities. Yet similar cases to those reported here have been described in the literature [17, 19, 20]. Therefore the true frequency of cochleovestibular disorders in patients with syphilis remains unknown. Among features which can explain the relative frequency of such cases, we first noticed the once again rising frequency of the affection [4, 5, 6, 9, 11,29, 30, 31, 32]. For instance in the United States the number of new cases reported each year (primary and secondary stages) was about 7000 in 1956 and 25,000 in 1975, which represents, according to Fleming and Brown, a quarter of the real cases. Similarly, a study performed in the dermatological department of our hospital [7] showed the same trend of increasing frequency. Such atypical forms of evolution seem to become more frequent than before, not exclusively for neurosyphilis [8]. The use of antibiotics, either to treat the venereal disease or to treat an intercurrent infectious disease, may play an important role. The dosage used may be sufficient to alter the usual picture of the disease but insufficient to prevent the subsequent course of the affection, in particular towards neurosyphilis. Finally, we consider today's physicians are less well trained to detect the disease and discreet signs may be missed. Thus our first patient received a regimen of antibiotic for venereal disease with no characteristic features of syphilis and but was considered to be gonorrhea. In conclusion, even if the syphilitic origin of isolated cochleovestibular involvement, without prior positive history of syphilis remains rare, this possibility should be kept in mind, in view of the actual frequency of atypical cases. It means that the occurrence of such an affection, especially in a young patient, is an indication to perform the necessary serological tests and a CSF examination, if any doubt exists and when another diagnosis cannot be made with absolute certainty. This advice is also available for several other neurological pictures.
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References 1. Aho, K., Sievers, K., Salo, O. P.: Late complications of syphilis. Acta dermat, venereol. 49, 336--342 (1969) 2. Atwood, W. G., Miller, L.: The TPI and FTA-ABS tests in treated late syphilis. J. Am. med. Assoc. 203, 549--551 (1968) 3. Beerman, H., Leslie, N., Schlamberg, I.: Syphilis. Arch. Int. Med. 109, 323--344 (1962) 4. Blattner, R. J.: Syphilis is still a problem. J. Pediat. 59,625--628 (1961) 5. Brown, W. J.: Studies in syphilis epidemiology. Brit. J. venereal Diseases 42, 110--115 (1966) 6. Brown, W. J.: A current look at venereal diseases. Current status of syphilis in the United States. Publ. Health Rep. 75, 990 (1960) 7. Cheseaux-Rithar, A.: Epidemiologie de la syphilis primaire et secondaire chez les malades hospitalis6s dans le service de dermatov6n~r6ologie de Lausanne de 1960 h 1973. Th~se M6decine de Lausanne 1976 8. Degos, R., Delzant, O.: Les aspects actuels de la syphilis r6cente. Bull. et m6moires des H6pitaux de Paris 113, 460--465 (1962) 9. Fleming, W. L., Brown, W. J.: National survey of venereal diseases treated by physicians in 1968. J. Am. med. Assoc. 211, 1827--1830 (1970) 10. Dewhurst, K.: Atypical serology in neurosyphilis. J. Neurol. Neurosurg. Psychiat. 31, 496--500 (1968) 11. King, A.: Failure to control venereal diseases. Brit. Med. J. 1970 I, 451--457 12. Kofman, O.: The changing pattern of neurosyphilis. Can. Med. Ass. J. 74, 807--812 (1956) 13. Le Henoff, G.: A p r o p o s de 3 cas de surdit6 par syphilis h6r6ditaire tardive. J. fran~ais d'ORL 7, 967--968 (1958) 14. Lloyd, J. H.: Syphilis of the eighth nerve. Arch. Neurol. Psychiat. 5, 617--618 (1921) 15. Locage, M., Cumings, J. N.: Cerebrospinal fluid in various diseases. Brit. Med. 3. 1958 I, 618--620 16. Lund, R.: Observations cliniques pour contribuer h &udier la question de la neurolabyrinthite syphilitique. Acta oto-laryng. (Stockh.) 3, 331--347 (1932) 17. Merrit, H. H., Adams, R. D., Salomon, H. C.: Neurosyphilis. New York: Oxford 1946 18. Mourier-Kuhn, P., Gaillard, J., Morgon, A.: La syphilis en oto-rhino-laryngologie; &at actuel dans un service hospitalier. J. franqais d'ORL 7, 883--886 (1958) 19. Pellegrini, G., Orsini, P., de Frimas, J. L., et al.: Surdit6 bilat6rale rapidement progressive par neurolabyrinthite syphilitique. Revue d'oto-neuro-ophtalmologie 41, 203--310 (1969) 20. Poilpr6, E., Morin, P., Piton, M., et al.: Apropos de deux observations de syphilis auriculaire. Revue ONO 43, 136--140 (1971) 21. Portmann, M., Grimaldi, P.: La syphilis de l'oreille. Encyclop6die m6dico-chirurgicale 20240 A 10 22. Ramadier: La syphilis auriculaire. Doin 1928 23. Short, D. H., Knox, J.: Neurosyphilis, the search for adequate treatment. Arch. Dermat. (Chic.) 93, 87--91 (1966) 24. Spangler, A. S., Jackson, J., Fiumara, N. J.: Syphilis with a negative blood test reaction. J. Am. reed. Assoc. 189, 87--90 (1964) 25. Sparling, P. F.: Diagnosis and treatment of syphilis. New Engl. J. Med. 284,642--652 (1971) 26. Wagemann, W.: f3ber die Inkonstanz der vestibuliiren Befunde bei der Labyrintosyphilis. Z. laryngo. Rhinol. 37, 114--124 (1958) 27. Wagemann, W.: Audiologische Befunde bei luetischen Innenohrsch~iden. H.N.O. (Berl.) 4, 129--133 (1954) 28. Wyrsh, J.: Ober Neurolues. Praxis 42, 77--82 (1953) 29. World Health Statistics Report 28, 114--126; 420--426 (1975) 30. World Health Statistics Report 29,236--248 (1976) 31. World Health Statistics Report 22,309--321 (1969) 32. World Health Statistics Report 29, 236--239 (1976) 33. Persistance of treponema after treatment of syphilis. Lancet 1968 I, 717--719 Received May 1 l, 1978
J. Neurol. 219, 199--204 (1978) t~) by Springer-Vedag 1978
Cochleovestibular Involvement as the First Sign of Syphilis J. P. Hungerbfihler and F. Regli Service de Neurologie du Centre hospitalier universitaire vaudois, CH-1011 Lausanne, Switzerland
Summary. Three cases of syphilis with cochleovestibular symptoms are reported. There was either cochlear or vestibular involvement in two cases and, in the third, cochlear and vestibular involvement together. The disorder was unilateral in all three. In one case ~there was a concurrent lesion of the oculomotor nerve which was the motive for consultation. There was no other s y m p t o m suggesting the diagnosis of syphilis in any case. The important features of diagnosis are discussed. Key words: Neurosyphilis - Cranial nerve lesions - Cochlear disorder Vestibular disorder.
Zusammenfassung.Es werden drei Fiille einer cochleo-vestibul~iren luetischen Erkrankung geschildert. Je einmal war lediglich die cochle~ire bzw. die vestibul~ire Funktion betroffen, w~ihrend im dritten Fall beide Funktionen beeintr~ichtigt waren. Die L~ision war immer einseitig. In einem Fall war noch der N. okulomotorius betroffen. Es waren keine anderen klinischen Zeichen der luetischen Affektion nachweisbar. Die diagnostischen, therapeutischen und pathogenetischen Aspekte dieser luetischen Komplikation werden am Schlul3 diskutiert.
Introduction We recently had the opportunity to observe three cases of neurosyphilis presenting initially with cochleovestibular symptoms, without a prior history of, or other symptoms suggesting syphilis. Our purpose is to remind the physician of the existence of such an etiology for cochleovestibular symptoms, which, even if rare, can be encountered in that isolated ~brm. Indeed, in view of the frequency of vascular, toxic, non-specific inflammator 3, auricular affections and of the general impression of a decline in the number of cases of syphilis, as well as a certain lack of interest in syphilis itself, and the changing pattern of syphilis, the syphilitic nature of an auricular affection may actually be missed by the physician in the absence of any other suggestive sign.
0340-5354/78/0219/0199/$ 01.20
200
J.P. Hungerbiihler and E Regti
Case Reports Case 1 A man aged 40 was in good health until July 1975, when nausea, vomiting, dizziness and gait disturbance occurred and forced him to stay in bed. One day later the symptoms disappeared, A few weeks later the same attack recurred lasting for the same period of time. In November 1975, he began to complain of diplopia on right lateral gaze and downward.
lnitial Examination (November 1975) revealed a man in generally good condition. On neurological examination there was incomplete paralysis of the left inferior oblique muscle but no hearing loss, or nystagmus. The gait showed a tendency to deviate to the right with closed eyes and there was some unsteadiness on Romberg test. The rest of the examination was normal. Otological examinatior~ revealed the effects of otitis media and vestibular dysfunction but no hearing loss.
"Laboratory Findings. Routine laboratory data, EEG, Doppler examination of the carotids, gammaencephalography and cisternography (isotopic) were all normal. Examination of the CSF revealed clear cerebrospinal fluid, 42/3 leucocytes with 55% lymphocytes and 45% moncytes, glucose 11 mg%, protein 48 rag% and non-specific inflammatory reaction on protein electrophoresis. Research of sarcoidosis was negative.
Syphilis Reactions. Blood: Kolmer and VDRL positive 1/~,Nelson and FTA-ABS tests positive:
CSF: Kolmer and VDRL negative, FTA-ABS test positive. Subsequent Course. The patient received penicillin therapy (exact description see below). Within the following months the diplopia disappeared, there was no relapse of dizziness and the levels of Kolmer and VDRL decreased.
Case 2 A patient of 46 years was in good health until the abrupt appearance of tinnitus in the left ear with progressive deafness on the same side occurring within a few hours.
lnitial Examination (March 1976) revealed a patient in good general condition. Neurological examination disclosed only decreased hearing in the left ear with the Rinne test positive bilaterally and the Weber test lateralized to the right, Otological examination revealed a bearing loss of 70 db at 8 000 HZ (perception type) in the left ear and no vestibular dysfunction.
Laboratory Findings. Routine laboratory data were normal. Examination of the CSF revealed clear cerebrospinal fluid, 6/3 leucocytes with 46% lymphocytes, 24% monocytes, 4% polynuclear cells, 26% lymphoplasmocytes, protein 32mg%, glucose 59mg% and on protein electrophoresis there was a slight elevation of gammaglobulins with elevation of IgG and IgM present.
Syphilitic Reactions. Blood: Kolmer and VDRL were positive (~), Nelson and FTA-ABS tests positive; CSF: Kolmer and VDRL negative, FTA-ABS test positive.
Subsequent Course. The patient received a course of penicillin. The hearing loss remained unchanged while the tinnitus disappeared. The levels of Kolmer and VDRL are decreasing.
Case 3 A patient aged 50, whose medical history included a cerebral concussion at the age of 20 and moderate hypertension known for several months, began to feel abnormally tired on 11 October 1976 and experienced nausea and vomiting; he also had a gait disturbance and clumsiness of the left hand.
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lnitial Physical Examination (December 1976) was within normal limits but on neurological examination, there was horizontal and rotatory nystagmus on right lateral gaze, a tendency to deviate to the left when upright and on Unterberger test, no apparent hearing loss and a discreet diminution of vibratory sense in the legs. Audiometric studies revealed a hearing loss of 50 db (perception type) in the left ear and vestibular examination disclosed dysfunction on the left side with caloric hyporeflexia and normal rotatory response. Laboratory Findings. Routine laboratory data were all normal. Rhumatoid, latex test, australian antigen, LE cells and antinuclear antibody were negative. Neurological laboratory data were also normal except for the CFS results: clear cerebrospinal fluid, 26/3 leucocytes with 51% lymphocytes, 41% monocytes, 7% plasma cells, 485/3 red cells, glucose 58 mg%, protein 65 mg%, abnormal normomastix, and on protein electrophoresis elevation of gammaglobulins, with IgG 15.6 mg% (N = 2 to 4 mg%), IgM 6.85 mg% (N = 0) on immunoelectrophoresis. Syphilitic Reactions. Blood: Kolmer and VDRL positive (~64), Nelson and FTA-ABS positive; CSF: Kolmer and VDRL positive (~4), Nelson and FTA-ABS positive. Subsequent Course. The patient received a course of penicillin. Within the following months the symptoms disappeared and his neurological status returned to normal (according to his physician). The level of Kolmer and VDRL has been decreasing. Treatment in each case consisted of penicillin therapy 2.4 Mo Penicillin G IM Penadur LA twice during 4 weeks after corticotherapy has been given for a few days in order to prevent a Herxheimer reaction. Regular Control of VDRL and Kolmer with examination of CSF have been programmed.
Comments The three p a t i e n t s s h o w e d features c o r r e s p o n d i n g to the classical d e s c r i p t i o n o f the i n v o l v e m e n t o f the eight nerve in syphilis [1, 12--14, 16--22, 26--28]. The first p a t i e n t h a d a r e c u r r e n t unilateral vestibular d i s o r d e r c h a r a c t e r i z e d b y vertigo, nausea, unsteadiness a n d a t e n d e n c y to deviate to the right. The second p a t i e n t h a d unilateral c o c h l e a r i n v o l v e m e n t with r a p i d l y progressing hearing loss. The t h i r d h a d features o f c o c h l e a r a n d vestibular lesions: nausea, vomiting, unsteadiness, t e n d e n c y to deviate to the left a n d on o t o l o g i c a l e x a m i n a t i o n h e a r i n g loss o f the p e r c e p t i o n type as well as dissociated vestibular p e r i p h e r a l d y s f u n c t i o n on the left side. As can easily be stated, there are not e n o u g h characteristic features in this s y m p t o m a t o l o g y to orient the diagnosis t o w a r d a syphilitic etiology. I n d e e d the i n v o l v e m e n t o f the eighth cranial nerve with syphilis presents no characteristic elements, consisting either o f dissociated d i s o r d e r (cochlear or vestibular) o r a s s o c i a t e d c o c h l e a r a n d v e s t i b u l a r involvement, which m a y be either unilateral o r b i l a t e r a l o c c u r r i n g a b r u p t l y or in a progressive way. The course m a y be r e m i t t e n t so that, if c o c h l e a r a n d vestibular involvement occur t o g e t h e r it is difficult to distinguish the d i s o r d e r f r o m Meni~re's disease. Sparse s y m p t o m a t o l o g y a n d s p o n t a n e o u s cures have also been r e p o r t e d . A m o n g features which can suggest the diagnosis is the occurrence o f such s y m p t o m s in a p a t i e n t often still y o u n g in otherwise g o o d c o n d i t i o n . H o w e v e r , this e t i o l o g y m u s t be distinguished f r o m o t h e r diseases such as viral d i s o r d e r s which are m u c h m o r e frequent, even in y o u n g people. The difficulty a n d the interesting fact in the three patients was the occurrence o f these s y m p t o m s w i t h o u t c o n c u r r e n t o r p r i o r signs o f syphilis. A n e x p l a n a t i o n
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of such an evolution could be the unawareness of the affection by the patient or the reluctance to confess it. Yet our patients denied having noticed prior symptoms, even after the diagnosis had been made known to them. Therefore we consider this symptomatology represents the true evolution of the three cases without other indications of syphilis, even if we cannot be absolutely certain. Such a course has been described several times [17, 19, 20, 22] and with or without prior signs of syphilis, the cochleovestibular involvement can be the first sign of neurosyphilis. This.involvement occurs most frequently in the first 18 months of the infection but can be encountered in the late stages [17]. Interesting too is the fact that the eighth cranial nerve is one of the most frequently involved beside the second, third, and seventh cranial nerves [17]. Not rarely the lesion of the eighth cranial nerve occurs with involvement of another cranial nerve (the most frequently involved are the seventh and the third) either simultaneously or successively, also suggesting the diagnosis; so our third patient had an oculomotor involvement which was the motive for consultation. The nature of the lesion of the eighth nerve [17, 19--22] is generally thought to be a neurolabyrinthitis which may involve either the nerve or the labyrinth. As mentioned above, this involvement may occur in different stages of the disease: in secondary, tertiary and tabetic stages as well as with congenital syphilis. In the secondary stage this neurolabyrinthitis seems to be a meningoneuritis localized to the sheath of the auricular nerve in association with vascular lesions, secondarly to the penetration of the treponema pallidum in the leptomeningeal space. There may be simultaneous involvement of other cranial nerves. In the tertiary stage, in addition to the meningoneuritis, primary inflammatory parenchymatous lesions affecting the labyrinth, the labyrinthine paths of their centers (polioencephalitis) and lesions secondary to the extension of middle ear involvement (otolabyrinthitis) have been proposed. Polioencephalitis arising from the meningoneuritis and denervative nervous lesions have been postulated in the tabetic stage. Some authors have also described a labyrinthine periostitis. In view of the pleocytosis and the involvement of another cranial nerve we think the first patient had a meningoneuritis. In the second patient the absence of pleocytosis and the isolated cochlear involvement could suggest a primary parenchymatous inflammatory lesion of the labyrinth. In the third patient, the CSF pleocytosis, the cochleovestibular involvement and the syphilitic tests all positive, in the absence of clinical signs of the tabetic stage, suggest a meningoneuritis, although another type of lesion is not ruled out. Regarding the clinical stage of the affection, it is extremely difficult to conclude, in the absence of any other sign of the disease. However, the most probable seems to be a secondary or tertiary stage in all our patients although, particularly in the third patient the beginning of tabes cannot be entirely excluded. Indeed a lesion of the eighth nerve may also be the first sign of tabes, even if it is probably extremely rare in such an isolated form. As stated above, the diagnosis of syphilis in these cases depends on serological tests and the CSF examination [2, 3, 23--25]. With our patients all syphilitic tests were positive in the blood. Yet, in CSF, if FTA-ABS test were all positive, V D R L and Kolmer were positive only once (Case 3). We think the negative result of these two tests in the CSF does not exclude the diagnosis in presence of a positive F T A -
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ABS test, for the FTA-ABS test appears to be the most sensitive and specific test attesting the penetration o f treponema pallidum in the CSF (9) with the very rare false positive results, usually with a type of affection practically excluded in these cases; on the other hand dissociated reactions particularly in the CSF have been described in proven cases of neurosyphilis [10, 19, 20, 33, 15]. The absence of the usual CSF pleocytosis in the second patient is still compatible with the diagnosis, especially if an isolated labyrinthine lesion is postulated, in the presence of a positive FTA-ABS test in the CSF. The unusual hypoglycorachia (I 1 rag%) in our first patient led us to search for several diseases which could have given such a result. But after other possible diagnoses were excluded, the positive results of the syphilitic tests and the favourable evolution after treatment are indicative of a syphilitic origin. However, in the first two cases in particular we cannot completely rule out the occurrence of two diseases, namely a latent neurosyphilis and another neurological involvement resolving spontaneously, although it seems unlikely. What is the frequency of such an evolution? It is not easy to answer this question. Even now public health data are incomplete, often based on partial or false information. Fleming and Brown estimated in two studies [5, 9] that 80% of cases of syphilis were treated by private physicians and only a quarter to a third of all cases were reported to the health authorities. Yet similar cases to those reported here have been described in the literature [17, 19, 20]. Therefore the true frequency of cochleovestibular disorders in patients with syphilis remains unknown. Among features which can explain the relative frequency of such cases, we first noticed the once again rising frequency of the affection [4, 5, 6, 9, 11,29, 30, 31, 32]. For instance in the United States the number of new cases reported each year (primary and secondary stages) was about 7000 in 1956 and 25,000 in 1975, which represents, according to Fleming and Brown, a quarter of the real cases. Similarly, a study performed in the dermatological department of our hospital [7] showed the same trend of increasing frequency. Such atypical forms of evolution seem to become more frequent than before, not exclusively for neurosyphilis [8]. The use of antibiotics, either to treat the venereal disease or to treat an intercurrent infectious disease, may play an important role. The dosage used may be sufficient to alter the usual picture of the disease but insufficient to prevent the subsequent course of the affection, in particular towards neurosyphilis. Finally, we consider today's physicians are less well trained to detect the disease and discreet signs may be missed. Thus our first patient received a regimen of antibiotic for venereal disease with no characteristic features of syphilis and but was considered to be gonorrhea. In conclusion, even if the syphilitic origin of isolated cochleovestibular involvement, without prior positive history of syphilis remains rare, this possibility should be kept in mind, in view of the actual frequency of atypical cases. It means that the occurrence of such an affection, especially in a young patient, is an indication to perform the necessary serological tests and a CSF examination, if any doubt exists and when another diagnosis cannot be made with absolute certainty. This advice is also available for several other neurological pictures.
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