Eur. Neurol. 18: 149-156 (1979)
Zoster Meningitis and Radiculomeningitis after Tick Bite Cytological Findings in Cerebrospinal Fluid H. Shoji and D. Dommasch Neurologische Universitätsklinik und Poliklinik Wurzburg (Director: Prof. H.G. Mertens), Wiirzburg
Key Words. Zoster meningitis • Radiculomeningitis after tick bite • CSF cells
Meningitis or pleocytosis of the cerebrospi nal fluid (CSF) accompanying herpes zoster is not uncommon. The patients complain rather of neuralgia and radicular pain than of menin geal signs such as headache and nuchal rigidity. Tire pathological changes in the ganglia and dorsal roots were established by autopsy cases of herpes zoster (6, 12, 29). Recently, varicella-zoster virus (VZV) has been demon strated in the cranial and spinal ganglia (4,9,10, 20,26). As to the pathogenesis of zoster meningi tis, it is presumed that VZV spreads to the meninges and CSF from the ganglionitis (27). Radiculomyelomeningitis with erythema after tick bite (radiculomeningitis after tick
bite; 24. 25) has been observed in West Ger many, especially in the surroundings of Wurz burg, and might be caused by arbovirus B (1, 18, 19, 24, 25). The patients have histories of tick bite and erythema. After an incubation period, severe radicular pain occurs in the seg ments corresponding to the bite region and erythema. Segmental paresis or hypesthesia are often found, with moderate pleocytosis of the CSF. Occasionally, pyramidal signs may be observed. The radicular pain strongly suggests the in volvement of the dorsal roots, including ganglia. It may be speculated that this meningitis or pleocytosis of the CSF develops from the focus
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Abstract. Cytological changes in 9 samples of cerebrospinal fluid (CSF) from 5 patients with zoster meningitis and 12 samples from 5 patients with radiculomeningitis after tick bite were examined. 5 days after the onset of the skin eruption, the CSF cells in zoster meningitis consisted of many mononuclear blast forms — large lymphocytes and ‘immature’ plasma cells. 11 —15 days after the onset of the skin rash, they were replaced by small lymphocytes, some ‘mature’ plasma cells and monohistiocytes. In radiculomeningitis after tick bite, however, the CSF cells examined 10-21 days after the onset of radicular pain consisted of many large lymphocytes, immature plasma cells and a few neutrophils. From these findings, it might be suggested that the acute meningeal reaction of zoster meningitis subsides within about 1 week after the onset of the skin rash, but that of radiculomeningitis after tick bite continues at least for 2—3 weeks after the onset of radicular pain.
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of the dorsal roots, which is compatible with tire pathogenesis of zoster meningitis. There fore, it seemed to be of interest to compare the clinical aspects and CSF findings in both dis eases. Erbsldh and Kohlmeyer (8) discussed similar clinical findings in zoster meningitis and radiculomeningitis after tick bite. In this investigation, the CSF specimens from these diseases were examined by cytological methods. Morphological findings were com pared with the results of autoradiographic examinations (7). The pathophysiology in both forms of meningitis is discussed.
Materials and Methods Patients 9 samples of CSF from 5 patients with zoster men ingitis and 12 samples of CSF from 5 patients with radiculomeningitis after tick bite were studied. The clinical data were analyzed by charts. Cases and
clinical signs (meningeal irritation and other neurologi cal signs) are listed in table I. 5 patients had meningitis or pleocytosis of the CSF associated with herpes zoster between 1973 and 1975. They had no systemic disease such as leukemia. Case 2 showed the unusual clinical sign of a contralateral palsy in the hand. 3 of the patients revealed a high serum CF titer against VZV. 5 patients had tick bites (cases 7 and 8) or a sting by a wasp (cases 6 and 10) and erythema in June to August, 1975. In case 9, the history of a tick bite or a sting by a wasp was not clear. Severe radicular pain followed during 3 weeks to 2 months after the tick bite and erythema (case 6: 4 weeks, case 7: 7 weeks, case 8: 4 weeks, case 9: 2 3 weeks?, case 10: 3 weeks). Segmental paresis or hypesthesia was observed, with moderate pleocytosis in the CSF. These patients revealed no pyramidal tract sign. In 3 of them, no serum CF titer against Russian spring-summer encephalitis virus (HYPR strain) was detected. In order to compare CSF findings at similar stages of both diseases, a skin rash was assumed to be the initial sign of zoster meningitis, while the appearance of radicular pain clearly marked the beginning of radiculomeningitis after tick bite.
Table I. Cases and clinical signs Sex
Skin rash or radicular pain
Zoster meningitis M 1 25 l-Th-9 M 2 33 l-Th-9 3 16 M l-V-2 4 44 M r-C-2 5 38 M l-V-1 Radiculomeningitis after tick bite M 6 40 l-lumbar region 7 64 F r-lumbar region
Fever
Headache
Nuchal rigidity
Focal neurologic symptoms
+
+ -
±
-
l-Th-9 hypesthesia r-hand paresis
+
-
-
± ±
—
± +
-
-
+ —
+
-
8 9
55 66
M M
lumbar region lumbar region
+
-
10
58
M
l-lumbar region
±
—
r-facial palsy
—
—
l-Ieg paresis r-leg paresis with sensory disturbance l-L-4 syndrome Th-9,10,r-L-3,4 sensory disturbance 1-facial palsy Th-10 sensory disturbance
M - Male; F = female; I = left; r = right; V = trigeminal;C = cervical; Th = thoracic; L = lumbar.
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Table II. Cytological findings of CSF Cells/ Days mm3 after skin rash or radicular pain
Skin rash 1 5 15
492 93
2
11
95
3
11 20
4
5
Glucose CSF/blood mg/100 ml
N E L % % %
(LL) PC % %
(IPC) M % %
H %
O
(15) (0)
4 5
(2) (0)
11 10
2 7
36
61
(2)
4
(0)
31
4
117 30
90 48
3 76 66
(0) (0)
3 2
(0) (0)
16 28
2 4
14 32
113 51
36.4 32
61/128 54/73
87 83
(2) (0)
4 1
(0) (0)
6 11
3 5
30 60
53 22
53 48
60/89
1 77 88
(0) (0)
3 2
(0) (0)
16 10
3
573 511 239
162 225
57/96 40/74
4
84 90 3 87
(12) (4) (0)
5 4 0
(3) (1) (0)
6 5 9
1 1 1
70/103 66/96 60/73
2
46 73 75
GO) (2) (0)
7 4 2
(4) (1) (0)
43 22 19
2 1 4
59/94 50/122
5
56 72
(17) (0)
2 3
(1) (0)
20 17
17 8
74 93
(16) (0)
4 2
(2) (0)
14 4
7 1
EC
68 92
(12) (0)
7 1
(3) (0)
21 7
3
EC
55.8 33.5
85 75.5 55.8
43/80 52/73
10 27 38
83 81 43
8
19 30
93 71
9
14 30
212 20
72 61.5
61/111 68/83
1
21 30
154 21
102 54.6
66/89 78/83
1
10
LI1
Differential cell count
83 73
Radicular pain 14 6 30 60 7
Protein mg/100 ml
100 75
1
EC
4
4 2
5
N = Neutrophils; E = eosinophils; L = lymphocytes; LL = large lymphocytes;PC = plasma cells;IPC = immature plasma cells; M = monocytes; H = histiocytes; 0 = others; EC = ependymal cells. 1 LI of CSF cells examined by 3H-thymidine autoradiography (7).
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Case
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Zoster Meningitis and Radiculomeningitis after Tick Bite
Results
Cytological findings of CSF are shown in table II. Zoster Meningitis The specimen of case 1, taken 5 days after the onset of the skin rash, was dominated by many blast forms - large lymphocytes, imma ture plasma cells and monohistiocytes (fig. la). Tire CSF cells of the same case and 3 other cases, taken 15 and 11-14 days after the onset of the skin rash, were replaced by small lym phocytes with dark nuclei, mature plasma cells and monohistiocytes (fig. lb). In the CSF of case 5, taken 60 days after the onset of the skin
Fig. 1. CSF cells from zoster meningitis, a 5 days after the onset of the skin rash (case 1): large lympho cytes and immature plasma cells predominate, b 14 days after the onset of the skin rash (case 4): small lymphocytes and mature plasma cells. Fig. 2. CSF cells from radiculomeningitis after tick bite, 19 days (case 8; a) and 14 days (case 9; b) after the onset of radicular pain: many large lymphocytes and immature plasma cells. May-Griinwald-Giemsa. X 500.
rash, many ependymal cells, including some clusters, were observed among small lympho cytes and monohistiocytes. Radiculomeningitis after Tick Bite In the first CSF specimens of 5 cases, taken 10-21 days after the onset of radicular pain, many large lymphocytes, immature plasma cells and a few neutrophilic granulocytes were pres ent (fig. 2a, b). A monohistiocytic reaction was also observed in cases 7 and 8. In the second specimens of cases 6 and 7, taken 27 and 30 days after the onset of radicular pain, a few large lymphocytes and immature plasma cells were still present. However, the CSF cells from the third specimens of the same cases and the second specimens of 3 other cases, were all small lymphocytes, mature plasma cells and monohistiocytes. Ependymal cells or clusters were recognized in cases 9 and 10. Cells labeled with 3H-thymidine were ob served in all the autoradiographs of 5 CSF specimens. Most of the labeled cells of these CSF specimens were large lymphocytes, plasma cells including immature types and monocytes. In case 4 (zoster meningitis), the labeling index (LI) of the CSF cells 14 days after the onset of the skin rash was 1%. The autoradiograph of the first CSF specimen of case 10 (radiculomen ingitis after tick bite) showed 5% labeled cells. In the second specimens of cases 6 and 7, 27 and 30 days after the onset of radicular pain, 4% of the CSF cells could still be labeled (7).
Discussion
As to the CSF cells in viral meningitis, specimens taken at the acute to subacute stages are normally dominated by lymphocytes and plasma cells. However, the CSF cell types change during the course of the disease. In the
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Cytological Studies The sedimentations were prepared by Sayk's (23) method as modified by Bammer (2), and stained with May-Griinwald-Giemsa. For each specimen, the per centage of neutrophilic and eosinophilic granulocytes, lymphocytes, plasma cells, monocytes and histiocytes was determined. As to the lymphocytes and plasma cells, large lymphocytes and immature plasma cells were differentiated and counted separately. Plasma cells with large nuclei and deeply stained cytoplasms were regarded as immature types (22). An examina tion by ’H-thymidine autoradiography was performed on cells from 5 CSF specimens (1 case of zoster meningitis, 3 cases of radiculomeningitis after tick bite) in the different studies (7).
153
acute phase, blast forms — large or ‘trans formed’ lymphocytes and some plasma cells including ‘immature’ types - are observed in addition to the neutrophilic reaction. In the convalescent phase, these cells are replaced by small lymphocytes, ‘mature’ plasma cells and monohistiocytes (17, 21—23). Dommasch etal. (7), using 3H-thymidine autoradiography, re ported high (4—8%) CSF cell Lis in the acute phase of viral meningitis, and they pointed out that most of the labeled cells were large lym phocytes and plasma cells, mainly immature types. Ependymal cells were found in the CSF of cases 5, 9 and 10. These cells have been de scribed as target cells in mumps meningitis (13). The significance of ependymal cells in our series is unknown. Meningitis or pleocytosis of the CSF accom panying herpes zoster was reported to occur in about 30% of herpes zoster cases (5, 11). According to our experience (28), the CSF of 7 patients in the acute phase of trigeminal herpes zoster showed pleocytosis ranging between 12 and 120/mm3. In spite of moderate pleocytosis of the CSF, the patients hardly revealed any clinical sign of meningeal irritation. In this series (table I), meningeal signs also were clini cally uncertain. It appears that the signs of zoster meningitis are much milder than those of other viral meningitides, as, for example, mumps meningitis. The source of herpes zoster has been proved to be an infection of the cranial and spinal ganglia (4, 9, 10, 20, 26). From the autopsy cases, Denny-Brown et al. (6) described the findings of localized leptomeningitis, together with the inflammatory changes of the ganglia and dorsal roots, and mentioned that this focus was the origin of lymphocytosis in the CSF. It is presumed that zoster meningitis develops from the ganglionitis. In a case of zoster menin
Shoji/Dommasch
gitis, Shoji et al. (27), using immunofluores cence, demonstrated VZV antigens in CSF cells taken 8 days after the onset of the skin rash, but not in the CSF cells taken 11 days after the onset of the rash. In our case 1 of zoster meningitis, the CSF specimen taken 5 days after the onset of the skin rash showed many blast forms — large lymphocytes and immature plasma cells, which is considered to be a sign of acute viral menin gitis (21, 22). Tire CSF cells of the same case and of 3 other cases, taken 15 and 11—14 days, respectively, after the onset of the skin rash consisted of small lymphocytes, mature plasma cells and monohistiocytes, which is indicative of the convalescent phase. The LI of the CSF specimen of case 4 examined by autoradio graphy at 14 days after the onset of the skin rash was comparatively low (1%). From the cytological findings of the CSF, it might be suggested that the acute meningeal reaction of zoster meningitis subsides in the earlier phase after the skin rash. There is a peculiar radiculomeningitis after tick bite in the Wiiizburg area. Occasionally, encephalitis or myelitis of the same etiology are observed (1, 24, 25). Similar cases were report ed from other areas in West Germany (3, 8, 14-16). Zimmern and Gressthal viruses, which belong to the same group of arbovims B, were isolated (18, 19) from the ticks collected in that area. Unlike zoster infections (4, 9, 10, 20, 26), however, the presence of a causative agent has not yet been demonstrated in human dorsal roots and ganglia. The sickness occurs mostly from June to October, and in patients over 30 years of age. Tire patients have histories of tick bite or stings by wasps and erythema. After a variable incuba tion period, they suffer from severe radicular pain in the segments of the bite region and erythema. Segmental paresis or hypesthesia are
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154
155
Zoster Meningitis and Radiculomeningitis after Tick Bite
Acknowledgement We wish to thank Dr. K. Nagashima, Institute of Virology, Wurzburg, for valuable advice and discus sions, and Mrs. Frode for skilfull technical assis
tance. Dr. H. Shoji was supported by a scholarship of the Alexander von Humboldt Foundation which he wishes to acknowledge.
References 1 Bammcr, H. und Schenk, K.: Meningo-MyeloRadiculitis nach Zeckenbiss mit Erythem. Dt. Z. NervHeilk. 187: 25-34 (1965). 2 Bammer, H.: Zur Tumorzelldiagnostik im Liquor cerebrospinalis. Dt. Z. NervHeilk. 185: 89-109 (1963). 3 Bammer, H.: Weitere Beobachtungen über Neuroradikulomeningomyelitis nach Zecken- oder Arthropodenbiss in Hamburg und Umgebung; in Müller und Schaltenbrand, Arboviniscrkrankungen des Nervensystems in Europa, pp. 249-251 (Thieme, Stuttgart 1975). 4 Bastian, F.O.; Rabson, A.S., Yee, C.L., and Tralka, T.S.: Herpes-virus varicellae isolated from human dorsal root ganglia. Archs Path. 97: 331-333 (1974). 5 Carter, A.B.: Investigation into the effects of aurcomycin and chloramphenicol in herpes zoster. Br. med. J./V 987-991 (1951). 6 Denny-Brown, D.; Adams, R.D., and Fitzgerald, P.J.: Pathologic features of herpes zoster. A note on geniculate herpes. Archs Neurol. Psychiat., Lond.51: 216-231 (1944). 7 Dommasch, D.; Griininger, W., and Schultze, B.: Autoradiographic demonstration of proliferating cells in cerebrospinal fluid. J. Neurol. 214: 97-112 (1977). 8 Erbslöh, F. und Kohlmeyer, K.: Über polytope Erkrankungen des peripheren Nervensystems bei lymphozytärer Meningitis. Fortschr. Neurol. Psychiat. 36: 321-342 (1968). 9 Esiri, M.M. and Tomlinson, A.H.: Herpes zoster. Demonstration of virus in trigeminal nerve and ganglion by immunofluorescence and electron microscopy. J. neurol. Sei. 15: 35-48 (1972). 10 Ghatak, N.R. and Zimmerman, H.M.: Spinal gangli on in herpes zoster. Archs Path. 95: 411-415 (1973). 11 Grüner, K.: cited by Nasemann, T.: Der Zoster (Virologie und Klinik). Internist 6: 342-354 (1965).
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often found. Sometimes, a cranial nerve palsy, especially a bilateral facial palsy may occur. The cell counts in the CSF may be more or less increased. However, the patients may not show any clinical meningeal signs, just as in zoster meningitis. In our series, with the exception of case 6, clinical signs of meningeal irritation were hardly visible. Severe radicular pain exhibits a strong simi larity with zoster meningitis. It may be pre sumed that this meningitis or pleocytosis of the CSF develops from a focus in the dorsal roots including ganglia. In our series, tire CSF specimens of 5 cases, taken 10-21 days after the onset of radicular pain, contained many large lymphocytes, im mature plasma cells and a few neutrophils, which is diagnostic for the acute phase of viral meningitis. This is in striking contrast to the CSF cells taken 11 —15 days after the onset of the skin rash in zoster meningitis. Moreover, in 2 cases, the second CSF specimens, taken 27 and 30 days after the onset of radicular pain, still contained blast forms (LI :4%, morphologi cally, a few immature plasma cells). From these findings, it might be suggested that the acute meningeal reaction of this disease continues for 2—3 weeks after the onset of radicular pain, while in zoster meningitis it subsides within about 1 week after the appear ance of the skin rash. Further, it seems likely that the increase in CSF protein in radiculomeningitis after tick bite in our series also reflects a more severe radiculitis or an ‘allergic process’ as seen in Guillain-Barre syndrome.
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21 Oehmichen, M.: Cerebrospinal fluid cytology. An introduction and atlas (Thieme, Stuttgart 1976). 22 Peter, A.: The plasma cells of the cerebrospinal fluid. J. neurol. Sei. 4: 227-239 (1967). 23 Sayk, J.: Cytologie der Cerebrospinalflüssigkeit (Fischer, Jena 1960). 24 Schaltenbrand, G.: Radikulomyelomeningitis nach Zeckenbiss. Münch, med. Wschr. 18: 829-834 (1962). 25 Schaltenbrand, G.: Neuroradikulomyelitis und Erythema migrans in Franken; in Müller und Schaltenbrand, Arboviruserkrankungen des Nerven systems in Europa, pp. 154-188 (Thieme, Stutt gart 1975). 26 Shibuta, H.; Ishikawa, T.; Hondo, R.; Aoyama, Y.; Kurata, K., and Matumoto, M.: Varicella virus isolation from spinal ganglion. Arch. ges. Virus forsch. 45: 382-385 (1974). 27 Shoji, H.; Koya, M., and Ogiwara, H.: Meningitis associated with herpes zoster. Immunofluorescent demonstration of varicella-zoster antigens in CSF cells. J. Neurol. 213: 269-271 (1976). 28 Shoji, J.: Unpublished data. 29 Wohlwill, F.: Zur pathologischen Anatomie des Nervensystems beim Herpes zoster (auf Grund von zehn Sektionsfällen). Z. ges. Neurol. Psychiat. 89: 171-212 (1924).
Received: February 15, 1977 Accepted: August 14, 1978 Dr. H. Shoji, First Department of Internal Medicine, Kurumc University School of Medicine, Asahicho 67, 830-91 Kurume-city, Japan
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12 Head, H. and Campbell, A.W.: The pathology of herpes zoster and its bearing on sensory localisa tion. Brain 23: 353-523 (1900). 13 Herndon, R.M.; Johnson, R.T.; Davis, L.E., and Descalzi, L.R.: Ependymitis in mumps virus menin gitis. Electron microscopical studies of cerebro spinal fluid. Archs Neurol., Chicago 30: 475-479 (1974). 14 Hopf, H.Ch.: Epidemiologic dor Radikulomyclomeningitis mit Erythem nach Zeckenbiss in der Umbegung von Göttingen; in Müller und Schalten brand, Arboviruserkrankungen des Nervensystems in Europa, pp. 252-254 (Thieme, Stuttgart 1975). 15 Hörstrup, P. und Ackermann, R.: Beobachtungen zum klinischen Bild der durch Zecken übertragenen Meningopolyneuritis (Garin-Bujadoux, Bann warth); in Müller und Schaltenbrand, Arboviruser krankungen des Nervensystems in Europa, pp. 254-257 (Thieme, Stuttgart 1975). 16 Kohlmeyer, K.: Zur Klinik der typischen Zeckenviruserkrankungen in Zentraleuropa; in Müller und Schaltenbrand, Arboviruserkrankungen des Nerven systems in Europa, pp. 251-252 (Thieme, Stutt gart 1975). 17 Kölmel, H.W.: Atlas of cerebrospinal fluid cells (Springer, Berlin 1976). 18 Müller, W. und Bork, Ch.: Hämagglutinationshem mende Antikörper gegen ein aus Zecken neu iso liertes Virus in der gesunden Bevölkerung von Unterfranken. Z. Neurol. 198: 138-153 (1970). 19 Müller, W.K.: Das Zimmern-Virus und seine Unter stämme. Isolierung und vorläufige Charakterisie rung; in Müller und Schaltenbrand, Arboviruser krankungen des Nervensystems in Europa, pp. 47-55 (Thieme, Stuttgart 1975). 20 Nagashima, K.; Nakazawa, M.; Endo, H.; Kurata, T., and Aoyama, Y.: Pathology of the human spinal ganglia in varicella-zoster virus infection. Acta neuropath. 33: 105 117 (1975).
Zoster Meningitis and Radiculomeningitis after Tick Bite Cytological Findings in Cerebrospinal Fluid H. Shoji and D. Dommasch Neurologische Universitätsklinik und Poliklinik Wurzburg (Director: Prof. H.G. Mertens), Wiirzburg
Key Words. Zoster meningitis • Radiculomeningitis after tick bite • CSF cells
Meningitis or pleocytosis of the cerebrospi nal fluid (CSF) accompanying herpes zoster is not uncommon. The patients complain rather of neuralgia and radicular pain than of menin geal signs such as headache and nuchal rigidity. Tire pathological changes in the ganglia and dorsal roots were established by autopsy cases of herpes zoster (6, 12, 29). Recently, varicella-zoster virus (VZV) has been demon strated in the cranial and spinal ganglia (4,9,10, 20,26). As to the pathogenesis of zoster meningi tis, it is presumed that VZV spreads to the meninges and CSF from the ganglionitis (27). Radiculomyelomeningitis with erythema after tick bite (radiculomeningitis after tick
bite; 24. 25) has been observed in West Ger many, especially in the surroundings of Wurz burg, and might be caused by arbovirus B (1, 18, 19, 24, 25). The patients have histories of tick bite and erythema. After an incubation period, severe radicular pain occurs in the seg ments corresponding to the bite region and erythema. Segmental paresis or hypesthesia are often found, with moderate pleocytosis of the CSF. Occasionally, pyramidal signs may be observed. The radicular pain strongly suggests the in volvement of the dorsal roots, including ganglia. It may be speculated that this meningitis or pleocytosis of the CSF develops from the focus
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Abstract. Cytological changes in 9 samples of cerebrospinal fluid (CSF) from 5 patients with zoster meningitis and 12 samples from 5 patients with radiculomeningitis after tick bite were examined. 5 days after the onset of the skin eruption, the CSF cells in zoster meningitis consisted of many mononuclear blast forms — large lymphocytes and ‘immature’ plasma cells. 11 —15 days after the onset of the skin rash, they were replaced by small lymphocytes, some ‘mature’ plasma cells and monohistiocytes. In radiculomeningitis after tick bite, however, the CSF cells examined 10-21 days after the onset of radicular pain consisted of many large lymphocytes, immature plasma cells and a few neutrophils. From these findings, it might be suggested that the acute meningeal reaction of zoster meningitis subsides within about 1 week after the onset of the skin rash, but that of radiculomeningitis after tick bite continues at least for 2—3 weeks after the onset of radicular pain.
150
Shoji/Dommasch
of the dorsal roots, which is compatible with tire pathogenesis of zoster meningitis. There fore, it seemed to be of interest to compare the clinical aspects and CSF findings in both dis eases. Erbsldh and Kohlmeyer (8) discussed similar clinical findings in zoster meningitis and radiculomeningitis after tick bite. In this investigation, the CSF specimens from these diseases were examined by cytological methods. Morphological findings were com pared with the results of autoradiographic examinations (7). The pathophysiology in both forms of meningitis is discussed.
Materials and Methods Patients 9 samples of CSF from 5 patients with zoster men ingitis and 12 samples of CSF from 5 patients with radiculomeningitis after tick bite were studied. The clinical data were analyzed by charts. Cases and
clinical signs (meningeal irritation and other neurologi cal signs) are listed in table I. 5 patients had meningitis or pleocytosis of the CSF associated with herpes zoster between 1973 and 1975. They had no systemic disease such as leukemia. Case 2 showed the unusual clinical sign of a contralateral palsy in the hand. 3 of the patients revealed a high serum CF titer against VZV. 5 patients had tick bites (cases 7 and 8) or a sting by a wasp (cases 6 and 10) and erythema in June to August, 1975. In case 9, the history of a tick bite or a sting by a wasp was not clear. Severe radicular pain followed during 3 weeks to 2 months after the tick bite and erythema (case 6: 4 weeks, case 7: 7 weeks, case 8: 4 weeks, case 9: 2 3 weeks?, case 10: 3 weeks). Segmental paresis or hypesthesia was observed, with moderate pleocytosis in the CSF. These patients revealed no pyramidal tract sign. In 3 of them, no serum CF titer against Russian spring-summer encephalitis virus (HYPR strain) was detected. In order to compare CSF findings at similar stages of both diseases, a skin rash was assumed to be the initial sign of zoster meningitis, while the appearance of radicular pain clearly marked the beginning of radiculomeningitis after tick bite.
Table I. Cases and clinical signs Sex
Skin rash or radicular pain
Zoster meningitis M 1 25 l-Th-9 M 2 33 l-Th-9 3 16 M l-V-2 4 44 M r-C-2 5 38 M l-V-1 Radiculomeningitis after tick bite M 6 40 l-lumbar region 7 64 F r-lumbar region
Fever
Headache
Nuchal rigidity
Focal neurologic symptoms
+
+ -
±
-
l-Th-9 hypesthesia r-hand paresis
+
-
-
± ±
—
± +
-
-
+ —
+
-
8 9
55 66
M M
lumbar region lumbar region
+
-
10
58
M
l-lumbar region
±
—
r-facial palsy
—
—
l-Ieg paresis r-leg paresis with sensory disturbance l-L-4 syndrome Th-9,10,r-L-3,4 sensory disturbance 1-facial palsy Th-10 sensory disturbance
M - Male; F = female; I = left; r = right; V = trigeminal;C = cervical; Th = thoracic; L = lumbar.
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Case Age
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Table II. Cytological findings of CSF Cells/ Days mm3 after skin rash or radicular pain
Skin rash 1 5 15
492 93
2
11
95
3
11 20
4
5
Glucose CSF/blood mg/100 ml
N E L % % %
(LL) PC % %
(IPC) M % %
H %
O
(15) (0)
4 5
(2) (0)
11 10
2 7
36
61
(2)
4
(0)
31
4
117 30
90 48
3 76 66
(0) (0)
3 2
(0) (0)
16 28
2 4
14 32
113 51
36.4 32
61/128 54/73
87 83
(2) (0)
4 1
(0) (0)
6 11
3 5
30 60
53 22
53 48
60/89
1 77 88
(0) (0)
3 2
(0) (0)
16 10
3
573 511 239
162 225
57/96 40/74
4
84 90 3 87
(12) (4) (0)
5 4 0
(3) (1) (0)
6 5 9
1 1 1
70/103 66/96 60/73
2
46 73 75
GO) (2) (0)
7 4 2
(4) (1) (0)
43 22 19
2 1 4
59/94 50/122
5
56 72
(17) (0)
2 3
(1) (0)
20 17
17 8
74 93
(16) (0)
4 2
(2) (0)
14 4
7 1
EC
68 92
(12) (0)
7 1
(3) (0)
21 7
3
EC
55.8 33.5
85 75.5 55.8
43/80 52/73
10 27 38
83 81 43
8
19 30
93 71
9
14 30
212 20
72 61.5
61/111 68/83
1
21 30
154 21
102 54.6
66/89 78/83
1
10
LI1
Differential cell count
83 73
Radicular pain 14 6 30 60 7
Protein mg/100 ml
100 75
1
EC
4
4 2
5
N = Neutrophils; E = eosinophils; L = lymphocytes; LL = large lymphocytes;PC = plasma cells;IPC = immature plasma cells; M = monocytes; H = histiocytes; 0 = others; EC = ependymal cells. 1 LI of CSF cells examined by 3H-thymidine autoradiography (7).
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Case
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152 Shoji/Dommasch
Zoster Meningitis and Radiculomeningitis after Tick Bite
Results
Cytological findings of CSF are shown in table II. Zoster Meningitis The specimen of case 1, taken 5 days after the onset of the skin rash, was dominated by many blast forms - large lymphocytes, imma ture plasma cells and monohistiocytes (fig. la). Tire CSF cells of the same case and 3 other cases, taken 15 and 11-14 days after the onset of the skin rash, were replaced by small lym phocytes with dark nuclei, mature plasma cells and monohistiocytes (fig. lb). In the CSF of case 5, taken 60 days after the onset of the skin
Fig. 1. CSF cells from zoster meningitis, a 5 days after the onset of the skin rash (case 1): large lympho cytes and immature plasma cells predominate, b 14 days after the onset of the skin rash (case 4): small lymphocytes and mature plasma cells. Fig. 2. CSF cells from radiculomeningitis after tick bite, 19 days (case 8; a) and 14 days (case 9; b) after the onset of radicular pain: many large lymphocytes and immature plasma cells. May-Griinwald-Giemsa. X 500.
rash, many ependymal cells, including some clusters, were observed among small lympho cytes and monohistiocytes. Radiculomeningitis after Tick Bite In the first CSF specimens of 5 cases, taken 10-21 days after the onset of radicular pain, many large lymphocytes, immature plasma cells and a few neutrophilic granulocytes were pres ent (fig. 2a, b). A monohistiocytic reaction was also observed in cases 7 and 8. In the second specimens of cases 6 and 7, taken 27 and 30 days after the onset of radicular pain, a few large lymphocytes and immature plasma cells were still present. However, the CSF cells from the third specimens of the same cases and the second specimens of 3 other cases, were all small lymphocytes, mature plasma cells and monohistiocytes. Ependymal cells or clusters were recognized in cases 9 and 10. Cells labeled with 3H-thymidine were ob served in all the autoradiographs of 5 CSF specimens. Most of the labeled cells of these CSF specimens were large lymphocytes, plasma cells including immature types and monocytes. In case 4 (zoster meningitis), the labeling index (LI) of the CSF cells 14 days after the onset of the skin rash was 1%. The autoradiograph of the first CSF specimen of case 10 (radiculomen ingitis after tick bite) showed 5% labeled cells. In the second specimens of cases 6 and 7, 27 and 30 days after the onset of radicular pain, 4% of the CSF cells could still be labeled (7).
Discussion
As to the CSF cells in viral meningitis, specimens taken at the acute to subacute stages are normally dominated by lymphocytes and plasma cells. However, the CSF cell types change during the course of the disease. In the
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Cytological Studies The sedimentations were prepared by Sayk's (23) method as modified by Bammer (2), and stained with May-Griinwald-Giemsa. For each specimen, the per centage of neutrophilic and eosinophilic granulocytes, lymphocytes, plasma cells, monocytes and histiocytes was determined. As to the lymphocytes and plasma cells, large lymphocytes and immature plasma cells were differentiated and counted separately. Plasma cells with large nuclei and deeply stained cytoplasms were regarded as immature types (22). An examina tion by ’H-thymidine autoradiography was performed on cells from 5 CSF specimens (1 case of zoster meningitis, 3 cases of radiculomeningitis after tick bite) in the different studies (7).
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acute phase, blast forms — large or ‘trans formed’ lymphocytes and some plasma cells including ‘immature’ types - are observed in addition to the neutrophilic reaction. In the convalescent phase, these cells are replaced by small lymphocytes, ‘mature’ plasma cells and monohistiocytes (17, 21—23). Dommasch etal. (7), using 3H-thymidine autoradiography, re ported high (4—8%) CSF cell Lis in the acute phase of viral meningitis, and they pointed out that most of the labeled cells were large lym phocytes and plasma cells, mainly immature types. Ependymal cells were found in the CSF of cases 5, 9 and 10. These cells have been de scribed as target cells in mumps meningitis (13). The significance of ependymal cells in our series is unknown. Meningitis or pleocytosis of the CSF accom panying herpes zoster was reported to occur in about 30% of herpes zoster cases (5, 11). According to our experience (28), the CSF of 7 patients in the acute phase of trigeminal herpes zoster showed pleocytosis ranging between 12 and 120/mm3. In spite of moderate pleocytosis of the CSF, the patients hardly revealed any clinical sign of meningeal irritation. In this series (table I), meningeal signs also were clini cally uncertain. It appears that the signs of zoster meningitis are much milder than those of other viral meningitides, as, for example, mumps meningitis. The source of herpes zoster has been proved to be an infection of the cranial and spinal ganglia (4, 9, 10, 20, 26). From the autopsy cases, Denny-Brown et al. (6) described the findings of localized leptomeningitis, together with the inflammatory changes of the ganglia and dorsal roots, and mentioned that this focus was the origin of lymphocytosis in the CSF. It is presumed that zoster meningitis develops from the ganglionitis. In a case of zoster menin
Shoji/Dommasch
gitis, Shoji et al. (27), using immunofluores cence, demonstrated VZV antigens in CSF cells taken 8 days after the onset of the skin rash, but not in the CSF cells taken 11 days after the onset of the rash. In our case 1 of zoster meningitis, the CSF specimen taken 5 days after the onset of the skin rash showed many blast forms — large lymphocytes and immature plasma cells, which is considered to be a sign of acute viral menin gitis (21, 22). Tire CSF cells of the same case and of 3 other cases, taken 15 and 11—14 days, respectively, after the onset of the skin rash consisted of small lymphocytes, mature plasma cells and monohistiocytes, which is indicative of the convalescent phase. The LI of the CSF specimen of case 4 examined by autoradio graphy at 14 days after the onset of the skin rash was comparatively low (1%). From the cytological findings of the CSF, it might be suggested that the acute meningeal reaction of zoster meningitis subsides in the earlier phase after the skin rash. There is a peculiar radiculomeningitis after tick bite in the Wiiizburg area. Occasionally, encephalitis or myelitis of the same etiology are observed (1, 24, 25). Similar cases were report ed from other areas in West Germany (3, 8, 14-16). Zimmern and Gressthal viruses, which belong to the same group of arbovims B, were isolated (18, 19) from the ticks collected in that area. Unlike zoster infections (4, 9, 10, 20, 26), however, the presence of a causative agent has not yet been demonstrated in human dorsal roots and ganglia. The sickness occurs mostly from June to October, and in patients over 30 years of age. Tire patients have histories of tick bite or stings by wasps and erythema. After a variable incuba tion period, they suffer from severe radicular pain in the segments of the bite region and erythema. Segmental paresis or hypesthesia are
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Zoster Meningitis and Radiculomeningitis after Tick Bite
Acknowledgement We wish to thank Dr. K. Nagashima, Institute of Virology, Wurzburg, for valuable advice and discus sions, and Mrs. Frode for skilfull technical assis
tance. Dr. H. Shoji was supported by a scholarship of the Alexander von Humboldt Foundation which he wishes to acknowledge.
References 1 Bammcr, H. und Schenk, K.: Meningo-MyeloRadiculitis nach Zeckenbiss mit Erythem. Dt. Z. NervHeilk. 187: 25-34 (1965). 2 Bammer, H.: Zur Tumorzelldiagnostik im Liquor cerebrospinalis. Dt. Z. NervHeilk. 185: 89-109 (1963). 3 Bammer, H.: Weitere Beobachtungen über Neuroradikulomeningomyelitis nach Zecken- oder Arthropodenbiss in Hamburg und Umgebung; in Müller und Schaltenbrand, Arboviniscrkrankungen des Nervensystems in Europa, pp. 249-251 (Thieme, Stuttgart 1975). 4 Bastian, F.O.; Rabson, A.S., Yee, C.L., and Tralka, T.S.: Herpes-virus varicellae isolated from human dorsal root ganglia. Archs Path. 97: 331-333 (1974). 5 Carter, A.B.: Investigation into the effects of aurcomycin and chloramphenicol in herpes zoster. Br. med. J./V 987-991 (1951). 6 Denny-Brown, D.; Adams, R.D., and Fitzgerald, P.J.: Pathologic features of herpes zoster. A note on geniculate herpes. Archs Neurol. Psychiat., Lond.51: 216-231 (1944). 7 Dommasch, D.; Griininger, W., and Schultze, B.: Autoradiographic demonstration of proliferating cells in cerebrospinal fluid. J. Neurol. 214: 97-112 (1977). 8 Erbslöh, F. und Kohlmeyer, K.: Über polytope Erkrankungen des peripheren Nervensystems bei lymphozytärer Meningitis. Fortschr. Neurol. Psychiat. 36: 321-342 (1968). 9 Esiri, M.M. and Tomlinson, A.H.: Herpes zoster. Demonstration of virus in trigeminal nerve and ganglion by immunofluorescence and electron microscopy. J. neurol. Sei. 15: 35-48 (1972). 10 Ghatak, N.R. and Zimmerman, H.M.: Spinal gangli on in herpes zoster. Archs Path. 95: 411-415 (1973). 11 Grüner, K.: cited by Nasemann, T.: Der Zoster (Virologie und Klinik). Internist 6: 342-354 (1965).
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often found. Sometimes, a cranial nerve palsy, especially a bilateral facial palsy may occur. The cell counts in the CSF may be more or less increased. However, the patients may not show any clinical meningeal signs, just as in zoster meningitis. In our series, with the exception of case 6, clinical signs of meningeal irritation were hardly visible. Severe radicular pain exhibits a strong simi larity with zoster meningitis. It may be pre sumed that this meningitis or pleocytosis of the CSF develops from a focus in the dorsal roots including ganglia. In our series, tire CSF specimens of 5 cases, taken 10-21 days after the onset of radicular pain, contained many large lymphocytes, im mature plasma cells and a few neutrophils, which is diagnostic for the acute phase of viral meningitis. This is in striking contrast to the CSF cells taken 11 —15 days after the onset of the skin rash in zoster meningitis. Moreover, in 2 cases, the second CSF specimens, taken 27 and 30 days after the onset of radicular pain, still contained blast forms (LI :4%, morphologi cally, a few immature plasma cells). From these findings, it might be suggested that the acute meningeal reaction of this disease continues for 2—3 weeks after the onset of radicular pain, while in zoster meningitis it subsides within about 1 week after the appear ance of the skin rash. Further, it seems likely that the increase in CSF protein in radiculomeningitis after tick bite in our series also reflects a more severe radiculitis or an ‘allergic process’ as seen in Guillain-Barre syndrome.
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21 Oehmichen, M.: Cerebrospinal fluid cytology. An introduction and atlas (Thieme, Stuttgart 1976). 22 Peter, A.: The plasma cells of the cerebrospinal fluid. J. neurol. Sei. 4: 227-239 (1967). 23 Sayk, J.: Cytologie der Cerebrospinalflüssigkeit (Fischer, Jena 1960). 24 Schaltenbrand, G.: Radikulomyelomeningitis nach Zeckenbiss. Münch, med. Wschr. 18: 829-834 (1962). 25 Schaltenbrand, G.: Neuroradikulomyelitis und Erythema migrans in Franken; in Müller und Schaltenbrand, Arboviruserkrankungen des Nerven systems in Europa, pp. 154-188 (Thieme, Stutt gart 1975). 26 Shibuta, H.; Ishikawa, T.; Hondo, R.; Aoyama, Y.; Kurata, K., and Matumoto, M.: Varicella virus isolation from spinal ganglion. Arch. ges. Virus forsch. 45: 382-385 (1974). 27 Shoji, H.; Koya, M., and Ogiwara, H.: Meningitis associated with herpes zoster. Immunofluorescent demonstration of varicella-zoster antigens in CSF cells. J. Neurol. 213: 269-271 (1976). 28 Shoji, J.: Unpublished data. 29 Wohlwill, F.: Zur pathologischen Anatomie des Nervensystems beim Herpes zoster (auf Grund von zehn Sektionsfällen). Z. ges. Neurol. Psychiat. 89: 171-212 (1924).
Received: February 15, 1977 Accepted: August 14, 1978 Dr. H. Shoji, First Department of Internal Medicine, Kurumc University School of Medicine, Asahicho 67, 830-91 Kurume-city, Japan
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12 Head, H. and Campbell, A.W.: The pathology of herpes zoster and its bearing on sensory localisa tion. Brain 23: 353-523 (1900). 13 Herndon, R.M.; Johnson, R.T.; Davis, L.E., and Descalzi, L.R.: Ependymitis in mumps virus menin gitis. Electron microscopical studies of cerebro spinal fluid. Archs Neurol., Chicago 30: 475-479 (1974). 14 Hopf, H.Ch.: Epidemiologic dor Radikulomyclomeningitis mit Erythem nach Zeckenbiss in der Umbegung von Göttingen; in Müller und Schalten brand, Arboviruserkrankungen des Nervensystems in Europa, pp. 252-254 (Thieme, Stuttgart 1975). 15 Hörstrup, P. und Ackermann, R.: Beobachtungen zum klinischen Bild der durch Zecken übertragenen Meningopolyneuritis (Garin-Bujadoux, Bann warth); in Müller und Schaltenbrand, Arboviruser krankungen des Nervensystems in Europa, pp. 254-257 (Thieme, Stuttgart 1975). 16 Kohlmeyer, K.: Zur Klinik der typischen Zeckenviruserkrankungen in Zentraleuropa; in Müller und Schaltenbrand, Arboviruserkrankungen des Nerven systems in Europa, pp. 251-252 (Thieme, Stutt gart 1975). 17 Kölmel, H.W.: Atlas of cerebrospinal fluid cells (Springer, Berlin 1976). 18 Müller, W. und Bork, Ch.: Hämagglutinationshem mende Antikörper gegen ein aus Zecken neu iso liertes Virus in der gesunden Bevölkerung von Unterfranken. Z. Neurol. 198: 138-153 (1970). 19 Müller, W.K.: Das Zimmern-Virus und seine Unter stämme. Isolierung und vorläufige Charakterisie rung; in Müller und Schaltenbrand, Arboviruser krankungen des Nervensystems in Europa, pp. 47-55 (Thieme, Stuttgart 1975). 20 Nagashima, K.; Nakazawa, M.; Endo, H.; Kurata, T., and Aoyama, Y.: Pathology of the human spinal ganglia in varicella-zoster virus infection. Acta neuropath. 33: 105 117 (1975).
