Originalia J. Kohler, T. Winkler, A. K. Wakhloo
Listeria Brainstem Encephalitis: Two Own Cases and Literature Review Summary: We analysed two of our own and 21 patients described in the literature with listeria brainstem encephalitis. The disease was characterised by a prodromal state with fever, nausea and headache followed by severe brainstem dysfunction with multiple cranial nerve palsies, ataxia, respiratory insufficiency and coma. The diagnosis was established by isolation of Listeria monocytogenes from CSF and/or serum. Serological tests are without diagnostic evidence. Cerebrospinal fluid examination may not initially point to a bacterial infection. Computed tomography and magnetic resonance imaging technique might supply evidence of brainstem involvement and contribute to an early diagnosis. There is a high percentage of lethal outcome without early antibiotic therapy. Zusammenfassung: Listerien-Hirnstamm-Encephalitis. Auf der Basis einer Analyse von zwei eigenen und 21 Fallberichten aus der Literatur wird fiber die Klinik der Listerien-Hirnstamm-Encephalitis berichtet. Das Krankheitsbild ist gekennzeichnet durch ein uncharakteristisches Prodromalstadium gefolgt von multiplen Hirnnervenausffillen, cerebellfiren St6rungen und schwersten Hirnstammfunktionsausf~llen mit Ateminsuffizienz und Koma. Der Liquorbefund ist h~iufig uncharakteristisch und deutet vietfach nicht auf eine akute bakterielle Infektion hin. Bildgebende Verfahren, insbesondere die Magnetresonanztomografie, erlauben in der Frfihphase der Erkrankung den Nachweis einer Hirnstammbeteiligung. Die Diagnose wird durch den bakteriologischen Nachweis von Listeria monocytogenes aus Blut und/oder Liquor gesichert. Serotogische Verfahren sind nicht zuverlfissig. Ohne friihzeitige adfiquate antibiotische Therapie ist die Prognose der Listerien-Hirnstamm-Encephalitis sehr ungfinstig.
Introduction Listeria monocytogenes (LM) infections can take a variable course, ranging from practically no noticeable symptoms to severe affection of several organs often with a lethal outcome [1-5]. Particularly pregnant women and children are known to be at high risk of acquiring the infection. LM infection is considered to be one of the most frequent connatal infectious diseases [5]. Adults over the age of 45 and those with immunosuppression, e.g. malignant tumors, especially lymphomas, or undergoing immunosuppressive therapy are mostly affected [1-3, 6-11]. The mode of transmission cannot always be established. Transmission from man to man, and from animal (mainly sheep and 40 / 36
cattle are affected) to man has been observed through infection from contaminated faeces and by ingestion of contaminated food (cheese, milk). Serologic tests alone are without diagnostic evidence in listeriosis. A certain diagnosis can only be obtained by isolation of listeria from body fluids (blood, cerebrospinal fluid) or from biopsy of the affected organ. A particular manifestation of neurolisteriosis is known as listeria brainstem encephalitis. A detailed description of the disease with a comprehensive review of the literature is given.
Patients and Methods In addition to our own two cases, we analysed 21 other case histories taken from the literature between 1957 and 1989 with listeria brainstem encephalitis insofar as sufficient clinical, radiological and pathological data were available [12-29]. In all cases listeria infection had been proved microbiologically. The cases reported by Brun-Buisson et al. [30] and Zeman et al. [31] were excluded for lack of direct isolation of LM.
Results The present report concerns 15 male and eight female patients with a mean age of 48 years (range 24-69). In 7/23 patients an underlying disease (rheumatoid arthritis 2 x , Hodgkin's disease, non-Hodgkin's lymphoma, sarcoidosis, kidney transplant, alcoholism) was involved. Out of the seven patients four were receiving immunosuppressive therapy. Three patients developed listeria brainstem encephalitis a few days after surgical intervention (sclerosing of haemorrhoids, perianal abscess, tooth granuloma.) LM was detected in blood and in CSF culture in 14/23 and 10/23 patients, respectively. In two patients LM was detected in both. In one case LM could be identified immunogically by a specific listeria antibody [29]. The main clinical data are shown in detail in Table 1. In 19 out of 23 patients a prodromal state with nausea, vomiting, headache and fever has been observed. Nine out of 23 patients simultaneously showed meningitis with fever. Twenty-one out of 23 had cranial nerve deficits. In eighteen more than three cranial nerves were affected simultaneously. Additional cerebellar symptoms were common and found in 12/23 patients. Complex impairment of coordinated eye movements, involvement of the motor system and diabetes insipidus were comparatively rare. Received: 10 May 1990/Revision accepted: 5 October 1990 Dr. J. Kohler. Dr. T. Winkter,NeurologischeUniversit/itsklinik,Hansastr. 9, W-7800Freiburg, Dr, A. K. Wakhloo, RadiologischeUniversit~itsklinik, Abt. Neuroradiologie,Hauptstr. 5, W-7800 Freiburg, Germany.
Infection 19 (1991) No. 1 © MMV MedizinVerlag GmbH Mtinchen, Miinchen 1991
J. Kohler et al.: Listeria Brainstem Encephalitis Table 1: Clinical data of patients with listeria brainstem encephalitis (N = 23).
Prodromal state
19
(83)
9
(39)
21
(91)
21 19
(891) (83)
14 11 8 6 5
(61) (48) (35) (26) (21)
1
(4)
12
(52)
Gaze paralysis,internuclear ophthalmoplegia
4
(17)
Hemi-/paraparesis
3
(13)
Diabetes insipidus
2
(9)
Respiratory insufficiency,dysregulationof circulation, coma
17
(74)
Lethal outcome
11
(48)
Meningitis Cranial nerve deficits Nervus facialis Nervus glossopharyngeus Nervus trigeminusand Nervus vagus Nervus abducens Nervus hypoglossus Nervus oculomotorius Nervus vestibulocochlearis Nervus trochlearis and Nervus accessorius Ataxia, Dysarthria
Cerebrospinal Fluid The results of CSF analysis performed in 21/23 patients varied. There was a pleocytosis of approximately 310 cells/ mm3 (range 10-980) in 19/21 patients. Nine patients showed a predominance of mononuclear cells, especially lymphocytes, and eight a predominance of polymorphonuclear cells. Signs of blood-brain barrier dysfunction with mean elevated total protein content of 132 mg/dl (50-359 mg/dl) were observed in 14/17 patients. Evidence of intrathecal synthesis of immunoglobulins could be observed in none of the patients. Normal CSF data (cell count, protein level) were reported in the two cases of Delacour et al. [14].
Neuroimaging Pathological singns in cranial computed tomography were found in 4/11, in magnetic resonance imaging technique in 3/3 patients. Eleven out of 23 patients died. Necropsy was performed in seven cases [13, 15, 16, 26, 28, 32]. The clinical history of one of our own cases illustrates the typical course of listeria brainstem encephalitis.
Case Report A 52-year-old female office employee had suffered from
Figure 1: Magnetic resonance imaging technique (T 2 weighted) showing a lesion of increased signal intensity in brainstem near the base of the fourth ventricle.
mild polyarthritis for the past ten years. She never underwent immunosuppressive therapy. Beginning November 1988 she developed a burning pain and numbness of the right cheek. Severe neck pains led to chiropractic manipulation of the cervical spine. A few days after onset of symptoms acute dizziness, gait ataxia and vomiting developed. A week later in the hospital the patient showed symptoms including temperature of 39.5 C, bilateral loss of cranial nerve function V-VII, IX and X with concomitant vertigo, tendency to fall down towards the right side, hemihypaesthesia on right and singultus. Since computed tomography (CT) had indicated a possible tumor of the brainstem compressing the fourth ventricle, lumbar puncture was not performed because of the risk of herniation. Antibiotic therapy was initiated along with anti-edematous therapy with dexamethasone, since the possibility of inflammatory lesion was considered. In spite of the therapy the symptoms progressed with a critical rise in blood pressure and further cranial nerve involvement. CSF analysis showed a marked pleocytosis (430 cells/mm3), mainly lymphocytes and an elevated total protein (95 mg/dl). A second CT disclosed a circular lesion confined to the central part of pons with enhancement of contrast agent (Figure 1). Somatosensory evoked potentials from stimulation of the tibial nerves were pathologic with bilaterally prolonged P-40 latencies. The early acoustic evoked brainstem potentials were found to have abnormally prolonged interpeak latency I-V on both sides, representing a defect
Infection 19 (1991) No. 1 © MMV MedizinVerlag GmbH M~nchen, MiJnchen 1991
37 / 41
J. Kohler et al.: Listeria Brainstem Encephalitis
Figure 2: Computed tomography showing a lesion with circular contrast enhancement, perifocal edema and central hypodensity indicate abscess in the brainstem.
in brainstem conduction. Progressive respiratory insufficiency required mechanical ventilation. After isolation of LM from blood sample, cefotaxime was replaced by ampicillin (20 g/day) and netilmicin (100 mg/day). Listeria serology (CF) was still negative. Attempts to isolate the bacilli from CSF failed. The neurological deficits gradually improved and CSF values returned to almost normal. At the end of November only a residual pleocytosis of 9 cells/mm 3 with normal CSF protein was found. Magnetic resonance imaging (MRI) in January 1989 revealed a signal-intensive lesion 1 x 1.5 x 2 cm in diameter near the base of the fourth ventricle (Figure 2). The patient underwent rehabilitation training for several months, but dissociated sensory impairment and severe functional impairment of cranial nerves VI and VII remained. Discussion
The central nervous system is the most frequently affected organ in listeria infection presenting with meningitis and meningoencephalitis [1-3, 5, 33]. Eck was the first to describe involvement of the brainstem in listeria meningoencephalitis in 1957 [16]. In the following years similar cases were reported by Hirasawa [34] and Colmant [35]. Since then numerous other cases of listeria brainstem encephalitis have been reported [3, 12-15, 17-29, 32, 33, 36, 42 / 38
37, 39, 40-42], though the condition is regarded as a rare manifestation of LM infection. In recent years listeriosis has been diagnosed more often, especially in adults [3, 9], but detection of LM is quite difficult. Serological methods to establish the infection are not reliable. A great number of missed diagnoses have therefore to be taken into account. LM could be traced in necrotic material itself [40], in the leptomeninges, blood and CSF by bacteriological [16] and immunological methods [29]. Exact data regarding the frequency of listeria brainstem encephalitis are not available. Eck [16] found brainstem encephalitis in seven out of 11 patients in necropsy. Pollock et al. [33] reported "signs of brainstem encephalitis" in three out of 20 patients with listeria meningoencephalitis. Listeria brainstem encephalitis affects the middle-aged and the elderly. There is only one report of listeria brainstem encephalitis in neonates [35]. The predominance of males in our study was also observed by Nieman et al. in patients with neurolisteriosis [3]. We found an underlying disease causing some degree of immunodeficiency in 30% of the patients, corresponding with the findings of Nieman et al. [3]. It is particularly interesting that three patients developed symptoms following surgical intervention especially in the anorectal area [22, 23, 29]. One of them had also received immunosuppressive treatment. Since clinically asymptomatic carriers have been reported [2, 5, 9], the involvement of nervous system, resulting from listeria septicaemia from faecal or mouth contamination, appears possible [221. After a prodromal state listeria brainstem encephalitis is characterised by multiple cranial nerve palsies in combination with cerebellar signs. During the illness, which mostly took a rapidly deteriorating course, severe defects in brainstem functions, like respiratory insufficiency, central dysregulation of circulation and coma often developed. The clinical presentation of listeria brainstem encephalitis must be differentiated from a number of other possible diseases such as brainstem tumor, circulatory impairment, other bacteriological or viral inflammations, paraneoplastic syndromes, autoimmunological disorders and neoplastic meningeosis. Clinical presentation of listeriosis has changed over the past years [3]. Except in patients with human immunodeficiency virus infection LM seems to have become one of the most important causative agent of CNS infections in groups with immunodeficiency [3, 43, 44], though healthy individuals can be affected by the infection. In neurolisteriosis, focal encephalitis of brainstem and adjacent areas possibly presents the predominantly affected areas of the disease. Generally, clincal syndromes are inadequately classified in the literature. Thus under the term "meningitic syndrome", which is used in some of the case descriptions, symptoms clearly exceed those which can be attributed to classical
Infection 19 (1991)No. 1 © MMV Medizin Verlag GmbH Mtinchen, Miinchen 1991
J. K o h l e r et al.: Listeria B r a i n s t e m E n c e p h a l i t i s
meningitis, but rather indicate brainstem involvement [3, 4, 11]. In extremely rapidly deteriorating situations often with a lethal outcome, histopathological findings suggest the brainstem as the most affected region, even in the absence of adequate clinical symptoms [22, 29]. CSF findings are often uncharacteristic in cases of listeria brainstem encephalitis. Even in the meningitic state with severe cranial nerve involvement CSF may show only mild changes [21], or is still normal [14]. Cell count and cytology may not initially point to a bacterial infection. A limited number of neuroimaging data are available in patients with listeria brainstem encephalitis. The majority of computed tomographic (CT) investigations have been reported as normal until now. Delacour et al. [14] described edema of the brainstem. Lang et al. [22] and Rimailho et al. [24] found multiple hypodense areas of the brainstem and cerebellum. Low-density lesions with faint ring enhancement in cerebral hemispheres in early phase of neurolisteriosis were reported by Haykal et al. [45]. Cerebral abscesses in the hemispheres and basal ganglia visualized in CT have been considered as complications of neurolisteriosis [for review see 46]. Signs of brainstem abscess, observed in our patient (Figure 1), have not been described in the literature as yet. Magnetic resonance imaging (MRI) can now provide early evidence of brainstem involvement in inflammatory disease of the CNS [47]. MRI of our patient (Figure 2), later
performed in the course of the illness, showed a similar result to that described by Just et al. [20]. Antibiotic therapy is often withheld or delayed assuming a viral infection. Rapid progress of illness usually indicates a bacterial infection. Antibiotic therapy at this stage has often no therapeutic effect. Poor prognosis of listeria brainstem encephalitis with a lethal outcome in 48% of the noted cases seems to be due to late confirmation of diagnosis, and to absence of adequate treatment. Current drugs of choice are high dose ampicillin combined with aminoglycosides for several weeks [48]. New aspects concerning the histopathological findings compared with those described in the 1950s [16, 34, 35] have not been observed. The predominance of a focal, purulent, sometimes necrotising inflammation restricted to the brainstem and adjacent areas in addition to meningitis and ependymitis has been confirmed. There was no evidence of postinfectious demyelinisation as suggested earlier [18]. Patients with clinical signs of brainstem involvement, multiple cranial nerve dysfunction in particular, should be examined for possible listeria infection. After taking blood and CSF for cultures, immediately high-dose antibiotic therapy also with ampicillin should be started even without direct evidence of encephalitis, especially in those belonging to risk groups and patients with a febrile prodromal phase. MRI might supply evidence of brainstem lesions and contribute to an early diagnosis even before onset of clinical symptoms.
References
11. Stamm, A. M., Dismukes, W. E., Simmons, B. P., Cobbs, C. G., Eiliott, A., Budrich, P., Harmon, J.: Listeriosis in renal transplant recipients: report of an outbreak and review of 102 cases. Rev. Inf. Dis. 4 (1982) 665-682.
1. Gray, M. L., KiUinger, A. H.: Listeria monocytogenes and listeric infection. Bact. Rev. 30 (1966) 309-382. 2. Heck, A. F.: Listeria monocytogenes. In: Vinken, P. J., Bruyn, G. W. (eds.): Handbook of clinical neurology. Vol 33. Elsevier/North-Holland Publishing Company, Amsterdam-New York-Oxford 1978, pp. 77-95. 3. Nieman, R. E., Lorber, B.: Listeriosis in adults: a changing pattern: Report of eight cases and review of the literature 1968-1978. Rev. Infect. Dis. 2 (1980) 207-227. 4. Ringelmann, R., Stegmiiller, B., Franzen, H., Just, I.: Listeriose: Falldarstellung und Repetitorium. Immun. Infekt. 12 (1984) 89-93. 5. Schmidt-Wolf, G., Seeliger, H. P. R., Schretten-Brunner, A.: Menschliche Listeriose-Erkrankungen in der Bundesrepublik Deutschland 1969-1985. Zbl. Bakt. Hyg. A (1987) 472-486. 6. Gantz, N. M., Myerowitz, R. L., Medeiros, A. A.: Listeriosis in immunosuppressed patients. A cluster of eight cases. Am. J. Med. 58 (1975) 637-643. 7. Mossey, R. T., Sondheimer, J.: Listeriosis in patients with long-term hemodialysis and transfusional iron overload. Am. J. Med. 79 (1985) 397-400. 8. Salata, R. A., King, R. E., Gose, F., Pearson, 1L D.: Listeria monocytogenes cerebritis, bacteremia, and cutaneous lesions complicating hairy cell leukemia. Am. J. Med. 81 (1986) 1068-1072. 9. Seeliger, H. P. R., Emmerling, P., Emmerling, H.: Zur Verbreitung der Listeriose in Deutschland. Dtsch. Med. Wochenschr. 93 (1968) 2037-2043. 10. Simpson, J. F.: Listeria monocytogenes meningitis: an opportunistic infection. J.N.N.P. 34 (1971) 657-663.
12. Bourrin, J. C., Cohen, E., Chopard, J. L., Moulin, T., Trevoux, A.: Rhombencephalite list6rienne chez un malade non immund6prim6. Presse M6d. 17 (1988) 1317-1318. 13. Christ, P., Schiessl, R., Schoop, G.: Klinische und bakteriologische Beobachtungen bei vier Erkrankungen an Listeria-Meningoencephalitis. Dtsch. Archiv Klin. Med. 207 (1961) 223-238.
14. Delacour, J. L., Floriot, C., Ritz, A., Wagschal, G., Ory, J. P.:
15.
16. 17.
18. 19.
Rhombencephalites list6riennes sans atteinte m6ning6e. Presse M6d. 16 (1987) 735. Duff'y, P. E., Sassin, J. F., Summers, D. S., Lourie, H.: Rhombencephalitis due to Listeria rnonocytogenes. Neurology 14 (1964) 1067-1072. Eek, H.: Encephalomyelitis listeriaca apostemotosa. Schweiz. Med. Wsch. 87 (1957) 210-214. Ford, P. M., Herzberg, L., Ford, S. E.: Listeria monocytogenes: six cases affecting the central nervous system. Quarterly J. Med. 37 (1968) 281-290. Frith, R. W., Buchanan, P. R., Glasgow, G. L.: Listeria monocytogenes infection with rhombencephalitis. J.N.N.P. 50 (1987) 1383-1384. Howard, A. J., Kennard, C., Eykyn, S., Higgs, I.: Listerial infections of the central nervous system in the previously healthy adult. Infection 9 (1981) 80-84.
20. Just, M., Kr~imer, G., Higer, H. P., Thiimke, F., Pfannenstiel, P.: MRI of Listeria rhombencephalitis. Neuroradiology 29 (1987) 401-402.
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH Miinchen, Mtinchen 1991
39 / 43
J. Kohler et al.: Listeria Brainstem Encephalitis
21. Katz, R. I., MeGlamery, M. E., Levy, R.: CNS listeriosis: rhombencephalitis in a healthy immunocompetent person. Arch. Neurol. 36 (1979) 513-514.
22. Lang, B., Hirsch, F. W., Kiimmel, A., Keller, E, Anagnostopoulos, J., Just, H.: Infektion des ZNS durch Listeria monocytogenes. Immun. Infekt. 15 (1987) 175-178. 23. Mahony, J. F., Tambyah, J. A., Dalton, V. C., Wolfenden, W. H.: Pontomedullary listeriosis in renal allograft recipient. Br. Med. J. 2 (1974) 705.
24. Rimaiiho, A., Georges, J. L, Vassal, T., Pezzano, M, Richard, Ch., Auzepy, Ph.: Rhombenc6phatites list6rienne avec liquide cephatorachidien initial normal. Presse M6d. 17 (1988) 949-95t. 25. Safran, A. B., Berney, J., Rilliat, B.: L'ophtalmopl6gie internucl6aire dans les enc6phalites infectieuse: observation d'un cas de list6riose. Arch. Suisses Neurol. Neurochir. Psychiatr. 123 (1978) 179. 26. Trautmann, M., Wagner, M., Stoltenburg-Didinger, G., Briickner, O., Bringmann, A.: Rhombencephalitis durch Listeria monocytogenes: Klinische und pathologisch-anatomische Befunde bei einer seltenen Encephalitisform. Nervenarzt 53 (1982) 705, 27. Weinstein, A. J., Schiavone, W. A., Furlan, A. J.: Listeria rhombencephalitis-report of a case. Arch. Neurol. 39 (1982) 514-516. 28. Yersin, B. R., Glauser, M. P., Regli, F.: Infections ~tListeria monocytogenes chez l'adulte. Schweiz. Med. Wschr. 111 (1981) 1596-1602.
29. Zimmer C., Neuen-Jacob, E., M6bius, E., Benn, M., Wechsler, W.: Listeria monocytogenes - Ein ungew6hnlicher Fall einer Listerien-
Encephalitis bei einem gesunden erwachsenen Patienten. Akt. Neurol. 16 (1989) 107-109. 30. Brun-Buisson, C. J., de Gialluly, E , Gherardi, 1L, Otterbein, G.: Fatal nonmeningitic Listeria rhombencephalitis-report of two cases. Arch. Intern. Med. 145 (1985) 1982-1985. 31. Zeman, A., Bamford, J. M., Warlow, C. P , Mitchell, R. G.: Listeria encephalitis with intermittent symptoms and serological diagnosis. I.N.N.P. 51 (1988) 458~59. 32, Kocen, R. S., Mail', W. G. P., Findley, L J, Harvey, P. K. P., Perkin, O.: Brainstem encephalitis caused by Listeria monocytogenes infection. Int. Congress Series No. 472. In: Weinber~ A. N., Heck, A. F. (eds.), Excerpta Medica. Amsterdam-Oxford-New York 1977, p. 269.
44 / 40
33. Pollock, S. S., Pollock, T. M., Harrison, M. J. G.: Infection of the central nervous system by Listeria monocytogenes: a review of 54 adult and juvenile cases. Quarterly J. Med. 211 (1984) 331-340. 34. Hirasawa, H.: Morphologischer Beitrag zur Kenntnis der ListeriaMeningoencephalitis beim Erwachsenen und beim S~iugling. Arch. Psych. Nervenkrkh. 197 (1958) 449-462. 35. Colmant, H. J.: Neuropathologie der Listeriose. Dtsch. Zeitschrift Nervenheilkunde 182 (1961) 492-515. 36. Anonymus: Listeriosis. Br. Med. J. 2 (1971) 477-478. 37. Benazet, F., Sohier, R., Bonjean, M.: Les enc6phalites list6riennes suppur6es. Presse M6d. 65 (1957) 2168-2170. 38. Callea, L, Donati, E., Faggi, L , Sealzani, A., Callea, F.: Pontomedullary encephalitis and basal meningitis due to Listeria monocytogenes: report of a case. Eur. Neurol. 24 (1985) 217-220. 39. Hirsch, F. W., Drexler, H., Meinertz, T., Daschner, F.: Rhombencephalitis by Listeria rnonocytogenes: onset of symptoms two days after perianal injections. Infection 14 (1981) 151. 40. Kennard, C., Howard, A. J., Scholtz, C., Swash, M.: Infection of the brainstem by Listeria monocytogenes. I.N.N.P. 42 (1979) 931-933. 41. Pitner, S. E.: Listerial metencephalitis. South. Med. J. 59 (1966) 564-566. 42. Samson, M., Augustin, P., Verdure, L: A propos de deux cas de m6ningoenc6phalites list6rienne ~t forme bulbo-protub6rantielle. Soc. Fran~. Neurol. 125 (1971) 450-454. 43. Jacobs, J. L., Murray, H. W.: Why is Listeria monocytogenes not a pathogen in the acquired immunodeficiency syndrome? Arch. Intern. Med. 146 (1986) 1299-1300. 44. Mullin, G. E., Sheppell, A. L: Listeria monocytogenes and the acquired immunodeficiency syndrome. Arch. Intern. Med. 147 (1987) 176. 45. Haykal, H.: CT features of early Listeria monocytogenes cerebritis. A.J.N.R. 8 (1987) 279-282. 46. Dee, R. R., Lorber, B.: Brain abscess due to Listeria monocytogenes: Case report and literature review. Rev. Infect. Dis. 8 (1986) 968-977. 47. Davidson, H. D., Steiner, R. E.: MRI in infections of the central nervous system. A.J.N.R. 6 (1985) 499. 48. Marget, W., Seeliger, H. P. R.: Listeria rnonocytogenes infectionstherapeutic possibilities and problems. Infection 16 (Suppl. 2) (1988) 175-177.
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH Mtinchen, Miinchen 1991
Listeria Brainstem Encephalitis: Two Own Cases and Literature Review Summary: We analysed two of our own and 21 patients described in the literature with listeria brainstem encephalitis. The disease was characterised by a prodromal state with fever, nausea and headache followed by severe brainstem dysfunction with multiple cranial nerve palsies, ataxia, respiratory insufficiency and coma. The diagnosis was established by isolation of Listeria monocytogenes from CSF and/or serum. Serological tests are without diagnostic evidence. Cerebrospinal fluid examination may not initially point to a bacterial infection. Computed tomography and magnetic resonance imaging technique might supply evidence of brainstem involvement and contribute to an early diagnosis. There is a high percentage of lethal outcome without early antibiotic therapy. Zusammenfassung: Listerien-Hirnstamm-Encephalitis. Auf der Basis einer Analyse von zwei eigenen und 21 Fallberichten aus der Literatur wird fiber die Klinik der Listerien-Hirnstamm-Encephalitis berichtet. Das Krankheitsbild ist gekennzeichnet durch ein uncharakteristisches Prodromalstadium gefolgt von multiplen Hirnnervenausffillen, cerebellfiren St6rungen und schwersten Hirnstammfunktionsausf~llen mit Ateminsuffizienz und Koma. Der Liquorbefund ist h~iufig uncharakteristisch und deutet vietfach nicht auf eine akute bakterielle Infektion hin. Bildgebende Verfahren, insbesondere die Magnetresonanztomografie, erlauben in der Frfihphase der Erkrankung den Nachweis einer Hirnstammbeteiligung. Die Diagnose wird durch den bakteriologischen Nachweis von Listeria monocytogenes aus Blut und/oder Liquor gesichert. Serotogische Verfahren sind nicht zuverlfissig. Ohne friihzeitige adfiquate antibiotische Therapie ist die Prognose der Listerien-Hirnstamm-Encephalitis sehr ungfinstig.
Introduction Listeria monocytogenes (LM) infections can take a variable course, ranging from practically no noticeable symptoms to severe affection of several organs often with a lethal outcome [1-5]. Particularly pregnant women and children are known to be at high risk of acquiring the infection. LM infection is considered to be one of the most frequent connatal infectious diseases [5]. Adults over the age of 45 and those with immunosuppression, e.g. malignant tumors, especially lymphomas, or undergoing immunosuppressive therapy are mostly affected [1-3, 6-11]. The mode of transmission cannot always be established. Transmission from man to man, and from animal (mainly sheep and 40 / 36
cattle are affected) to man has been observed through infection from contaminated faeces and by ingestion of contaminated food (cheese, milk). Serologic tests alone are without diagnostic evidence in listeriosis. A certain diagnosis can only be obtained by isolation of listeria from body fluids (blood, cerebrospinal fluid) or from biopsy of the affected organ. A particular manifestation of neurolisteriosis is known as listeria brainstem encephalitis. A detailed description of the disease with a comprehensive review of the literature is given.
Patients and Methods In addition to our own two cases, we analysed 21 other case histories taken from the literature between 1957 and 1989 with listeria brainstem encephalitis insofar as sufficient clinical, radiological and pathological data were available [12-29]. In all cases listeria infection had been proved microbiologically. The cases reported by Brun-Buisson et al. [30] and Zeman et al. [31] were excluded for lack of direct isolation of LM.
Results The present report concerns 15 male and eight female patients with a mean age of 48 years (range 24-69). In 7/23 patients an underlying disease (rheumatoid arthritis 2 x , Hodgkin's disease, non-Hodgkin's lymphoma, sarcoidosis, kidney transplant, alcoholism) was involved. Out of the seven patients four were receiving immunosuppressive therapy. Three patients developed listeria brainstem encephalitis a few days after surgical intervention (sclerosing of haemorrhoids, perianal abscess, tooth granuloma.) LM was detected in blood and in CSF culture in 14/23 and 10/23 patients, respectively. In two patients LM was detected in both. In one case LM could be identified immunogically by a specific listeria antibody [29]. The main clinical data are shown in detail in Table 1. In 19 out of 23 patients a prodromal state with nausea, vomiting, headache and fever has been observed. Nine out of 23 patients simultaneously showed meningitis with fever. Twenty-one out of 23 had cranial nerve deficits. In eighteen more than three cranial nerves were affected simultaneously. Additional cerebellar symptoms were common and found in 12/23 patients. Complex impairment of coordinated eye movements, involvement of the motor system and diabetes insipidus were comparatively rare. Received: 10 May 1990/Revision accepted: 5 October 1990 Dr. J. Kohler. Dr. T. Winkter,NeurologischeUniversit/itsklinik,Hansastr. 9, W-7800Freiburg, Dr, A. K. Wakhloo, RadiologischeUniversit~itsklinik, Abt. Neuroradiologie,Hauptstr. 5, W-7800 Freiburg, Germany.
Infection 19 (1991) No. 1 © MMV MedizinVerlag GmbH Mtinchen, Miinchen 1991
J. Kohler et al.: Listeria Brainstem Encephalitis Table 1: Clinical data of patients with listeria brainstem encephalitis (N = 23).
Prodromal state
19
(83)
9
(39)
21
(91)
21 19
(891) (83)
14 11 8 6 5
(61) (48) (35) (26) (21)
1
(4)
12
(52)
Gaze paralysis,internuclear ophthalmoplegia
4
(17)
Hemi-/paraparesis
3
(13)
Diabetes insipidus
2
(9)
Respiratory insufficiency,dysregulationof circulation, coma
17
(74)
Lethal outcome
11
(48)
Meningitis Cranial nerve deficits Nervus facialis Nervus glossopharyngeus Nervus trigeminusand Nervus vagus Nervus abducens Nervus hypoglossus Nervus oculomotorius Nervus vestibulocochlearis Nervus trochlearis and Nervus accessorius Ataxia, Dysarthria
Cerebrospinal Fluid The results of CSF analysis performed in 21/23 patients varied. There was a pleocytosis of approximately 310 cells/ mm3 (range 10-980) in 19/21 patients. Nine patients showed a predominance of mononuclear cells, especially lymphocytes, and eight a predominance of polymorphonuclear cells. Signs of blood-brain barrier dysfunction with mean elevated total protein content of 132 mg/dl (50-359 mg/dl) were observed in 14/17 patients. Evidence of intrathecal synthesis of immunoglobulins could be observed in none of the patients. Normal CSF data (cell count, protein level) were reported in the two cases of Delacour et al. [14].
Neuroimaging Pathological singns in cranial computed tomography were found in 4/11, in magnetic resonance imaging technique in 3/3 patients. Eleven out of 23 patients died. Necropsy was performed in seven cases [13, 15, 16, 26, 28, 32]. The clinical history of one of our own cases illustrates the typical course of listeria brainstem encephalitis.
Case Report A 52-year-old female office employee had suffered from
Figure 1: Magnetic resonance imaging technique (T 2 weighted) showing a lesion of increased signal intensity in brainstem near the base of the fourth ventricle.
mild polyarthritis for the past ten years. She never underwent immunosuppressive therapy. Beginning November 1988 she developed a burning pain and numbness of the right cheek. Severe neck pains led to chiropractic manipulation of the cervical spine. A few days after onset of symptoms acute dizziness, gait ataxia and vomiting developed. A week later in the hospital the patient showed symptoms including temperature of 39.5 C, bilateral loss of cranial nerve function V-VII, IX and X with concomitant vertigo, tendency to fall down towards the right side, hemihypaesthesia on right and singultus. Since computed tomography (CT) had indicated a possible tumor of the brainstem compressing the fourth ventricle, lumbar puncture was not performed because of the risk of herniation. Antibiotic therapy was initiated along with anti-edematous therapy with dexamethasone, since the possibility of inflammatory lesion was considered. In spite of the therapy the symptoms progressed with a critical rise in blood pressure and further cranial nerve involvement. CSF analysis showed a marked pleocytosis (430 cells/mm3), mainly lymphocytes and an elevated total protein (95 mg/dl). A second CT disclosed a circular lesion confined to the central part of pons with enhancement of contrast agent (Figure 1). Somatosensory evoked potentials from stimulation of the tibial nerves were pathologic with bilaterally prolonged P-40 latencies. The early acoustic evoked brainstem potentials were found to have abnormally prolonged interpeak latency I-V on both sides, representing a defect
Infection 19 (1991) No. 1 © MMV MedizinVerlag GmbH M~nchen, MiJnchen 1991
37 / 41
J. Kohler et al.: Listeria Brainstem Encephalitis
Figure 2: Computed tomography showing a lesion with circular contrast enhancement, perifocal edema and central hypodensity indicate abscess in the brainstem.
in brainstem conduction. Progressive respiratory insufficiency required mechanical ventilation. After isolation of LM from blood sample, cefotaxime was replaced by ampicillin (20 g/day) and netilmicin (100 mg/day). Listeria serology (CF) was still negative. Attempts to isolate the bacilli from CSF failed. The neurological deficits gradually improved and CSF values returned to almost normal. At the end of November only a residual pleocytosis of 9 cells/mm 3 with normal CSF protein was found. Magnetic resonance imaging (MRI) in January 1989 revealed a signal-intensive lesion 1 x 1.5 x 2 cm in diameter near the base of the fourth ventricle (Figure 2). The patient underwent rehabilitation training for several months, but dissociated sensory impairment and severe functional impairment of cranial nerves VI and VII remained. Discussion
The central nervous system is the most frequently affected organ in listeria infection presenting with meningitis and meningoencephalitis [1-3, 5, 33]. Eck was the first to describe involvement of the brainstem in listeria meningoencephalitis in 1957 [16]. In the following years similar cases were reported by Hirasawa [34] and Colmant [35]. Since then numerous other cases of listeria brainstem encephalitis have been reported [3, 12-15, 17-29, 32, 33, 36, 42 / 38
37, 39, 40-42], though the condition is regarded as a rare manifestation of LM infection. In recent years listeriosis has been diagnosed more often, especially in adults [3, 9], but detection of LM is quite difficult. Serological methods to establish the infection are not reliable. A great number of missed diagnoses have therefore to be taken into account. LM could be traced in necrotic material itself [40], in the leptomeninges, blood and CSF by bacteriological [16] and immunological methods [29]. Exact data regarding the frequency of listeria brainstem encephalitis are not available. Eck [16] found brainstem encephalitis in seven out of 11 patients in necropsy. Pollock et al. [33] reported "signs of brainstem encephalitis" in three out of 20 patients with listeria meningoencephalitis. Listeria brainstem encephalitis affects the middle-aged and the elderly. There is only one report of listeria brainstem encephalitis in neonates [35]. The predominance of males in our study was also observed by Nieman et al. in patients with neurolisteriosis [3]. We found an underlying disease causing some degree of immunodeficiency in 30% of the patients, corresponding with the findings of Nieman et al. [3]. It is particularly interesting that three patients developed symptoms following surgical intervention especially in the anorectal area [22, 23, 29]. One of them had also received immunosuppressive treatment. Since clinically asymptomatic carriers have been reported [2, 5, 9], the involvement of nervous system, resulting from listeria septicaemia from faecal or mouth contamination, appears possible [221. After a prodromal state listeria brainstem encephalitis is characterised by multiple cranial nerve palsies in combination with cerebellar signs. During the illness, which mostly took a rapidly deteriorating course, severe defects in brainstem functions, like respiratory insufficiency, central dysregulation of circulation and coma often developed. The clinical presentation of listeria brainstem encephalitis must be differentiated from a number of other possible diseases such as brainstem tumor, circulatory impairment, other bacteriological or viral inflammations, paraneoplastic syndromes, autoimmunological disorders and neoplastic meningeosis. Clinical presentation of listeriosis has changed over the past years [3]. Except in patients with human immunodeficiency virus infection LM seems to have become one of the most important causative agent of CNS infections in groups with immunodeficiency [3, 43, 44], though healthy individuals can be affected by the infection. In neurolisteriosis, focal encephalitis of brainstem and adjacent areas possibly presents the predominantly affected areas of the disease. Generally, clincal syndromes are inadequately classified in the literature. Thus under the term "meningitic syndrome", which is used in some of the case descriptions, symptoms clearly exceed those which can be attributed to classical
Infection 19 (1991)No. 1 © MMV Medizin Verlag GmbH Mtinchen, Miinchen 1991
J. K o h l e r et al.: Listeria B r a i n s t e m E n c e p h a l i t i s
meningitis, but rather indicate brainstem involvement [3, 4, 11]. In extremely rapidly deteriorating situations often with a lethal outcome, histopathological findings suggest the brainstem as the most affected region, even in the absence of adequate clinical symptoms [22, 29]. CSF findings are often uncharacteristic in cases of listeria brainstem encephalitis. Even in the meningitic state with severe cranial nerve involvement CSF may show only mild changes [21], or is still normal [14]. Cell count and cytology may not initially point to a bacterial infection. A limited number of neuroimaging data are available in patients with listeria brainstem encephalitis. The majority of computed tomographic (CT) investigations have been reported as normal until now. Delacour et al. [14] described edema of the brainstem. Lang et al. [22] and Rimailho et al. [24] found multiple hypodense areas of the brainstem and cerebellum. Low-density lesions with faint ring enhancement in cerebral hemispheres in early phase of neurolisteriosis were reported by Haykal et al. [45]. Cerebral abscesses in the hemispheres and basal ganglia visualized in CT have been considered as complications of neurolisteriosis [for review see 46]. Signs of brainstem abscess, observed in our patient (Figure 1), have not been described in the literature as yet. Magnetic resonance imaging (MRI) can now provide early evidence of brainstem involvement in inflammatory disease of the CNS [47]. MRI of our patient (Figure 2), later
performed in the course of the illness, showed a similar result to that described by Just et al. [20]. Antibiotic therapy is often withheld or delayed assuming a viral infection. Rapid progress of illness usually indicates a bacterial infection. Antibiotic therapy at this stage has often no therapeutic effect. Poor prognosis of listeria brainstem encephalitis with a lethal outcome in 48% of the noted cases seems to be due to late confirmation of diagnosis, and to absence of adequate treatment. Current drugs of choice are high dose ampicillin combined with aminoglycosides for several weeks [48]. New aspects concerning the histopathological findings compared with those described in the 1950s [16, 34, 35] have not been observed. The predominance of a focal, purulent, sometimes necrotising inflammation restricted to the brainstem and adjacent areas in addition to meningitis and ependymitis has been confirmed. There was no evidence of postinfectious demyelinisation as suggested earlier [18]. Patients with clinical signs of brainstem involvement, multiple cranial nerve dysfunction in particular, should be examined for possible listeria infection. After taking blood and CSF for cultures, immediately high-dose antibiotic therapy also with ampicillin should be started even without direct evidence of encephalitis, especially in those belonging to risk groups and patients with a febrile prodromal phase. MRI might supply evidence of brainstem lesions and contribute to an early diagnosis even before onset of clinical symptoms.
References
11. Stamm, A. M., Dismukes, W. E., Simmons, B. P., Cobbs, C. G., Eiliott, A., Budrich, P., Harmon, J.: Listeriosis in renal transplant recipients: report of an outbreak and review of 102 cases. Rev. Inf. Dis. 4 (1982) 665-682.
1. Gray, M. L., KiUinger, A. H.: Listeria monocytogenes and listeric infection. Bact. Rev. 30 (1966) 309-382. 2. Heck, A. F.: Listeria monocytogenes. In: Vinken, P. J., Bruyn, G. W. (eds.): Handbook of clinical neurology. Vol 33. Elsevier/North-Holland Publishing Company, Amsterdam-New York-Oxford 1978, pp. 77-95. 3. Nieman, R. E., Lorber, B.: Listeriosis in adults: a changing pattern: Report of eight cases and review of the literature 1968-1978. Rev. Infect. Dis. 2 (1980) 207-227. 4. Ringelmann, R., Stegmiiller, B., Franzen, H., Just, I.: Listeriose: Falldarstellung und Repetitorium. Immun. Infekt. 12 (1984) 89-93. 5. Schmidt-Wolf, G., Seeliger, H. P. R., Schretten-Brunner, A.: Menschliche Listeriose-Erkrankungen in der Bundesrepublik Deutschland 1969-1985. Zbl. Bakt. Hyg. A (1987) 472-486. 6. Gantz, N. M., Myerowitz, R. L., Medeiros, A. A.: Listeriosis in immunosuppressed patients. A cluster of eight cases. Am. J. Med. 58 (1975) 637-643. 7. Mossey, R. T., Sondheimer, J.: Listeriosis in patients with long-term hemodialysis and transfusional iron overload. Am. J. Med. 79 (1985) 397-400. 8. Salata, R. A., King, R. E., Gose, F., Pearson, 1L D.: Listeria monocytogenes cerebritis, bacteremia, and cutaneous lesions complicating hairy cell leukemia. Am. J. Med. 81 (1986) 1068-1072. 9. Seeliger, H. P. R., Emmerling, P., Emmerling, H.: Zur Verbreitung der Listeriose in Deutschland. Dtsch. Med. Wochenschr. 93 (1968) 2037-2043. 10. Simpson, J. F.: Listeria monocytogenes meningitis: an opportunistic infection. J.N.N.P. 34 (1971) 657-663.
12. Bourrin, J. C., Cohen, E., Chopard, J. L., Moulin, T., Trevoux, A.: Rhombencephalite list6rienne chez un malade non immund6prim6. Presse M6d. 17 (1988) 1317-1318. 13. Christ, P., Schiessl, R., Schoop, G.: Klinische und bakteriologische Beobachtungen bei vier Erkrankungen an Listeria-Meningoencephalitis. Dtsch. Archiv Klin. Med. 207 (1961) 223-238.
14. Delacour, J. L., Floriot, C., Ritz, A., Wagschal, G., Ory, J. P.:
15.
16. 17.
18. 19.
Rhombencephalites list6riennes sans atteinte m6ning6e. Presse M6d. 16 (1987) 735. Duff'y, P. E., Sassin, J. F., Summers, D. S., Lourie, H.: Rhombencephalitis due to Listeria rnonocytogenes. Neurology 14 (1964) 1067-1072. Eek, H.: Encephalomyelitis listeriaca apostemotosa. Schweiz. Med. Wsch. 87 (1957) 210-214. Ford, P. M., Herzberg, L., Ford, S. E.: Listeria monocytogenes: six cases affecting the central nervous system. Quarterly J. Med. 37 (1968) 281-290. Frith, R. W., Buchanan, P. R., Glasgow, G. L.: Listeria monocytogenes infection with rhombencephalitis. J.N.N.P. 50 (1987) 1383-1384. Howard, A. J., Kennard, C., Eykyn, S., Higgs, I.: Listerial infections of the central nervous system in the previously healthy adult. Infection 9 (1981) 80-84.
20. Just, M., Kr~imer, G., Higer, H. P., Thiimke, F., Pfannenstiel, P.: MRI of Listeria rhombencephalitis. Neuroradiology 29 (1987) 401-402.
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH Miinchen, Mtinchen 1991
39 / 43
J. Kohler et al.: Listeria Brainstem Encephalitis
21. Katz, R. I., MeGlamery, M. E., Levy, R.: CNS listeriosis: rhombencephalitis in a healthy immunocompetent person. Arch. Neurol. 36 (1979) 513-514.
22. Lang, B., Hirsch, F. W., Kiimmel, A., Keller, E, Anagnostopoulos, J., Just, H.: Infektion des ZNS durch Listeria monocytogenes. Immun. Infekt. 15 (1987) 175-178. 23. Mahony, J. F., Tambyah, J. A., Dalton, V. C., Wolfenden, W. H.: Pontomedullary listeriosis in renal allograft recipient. Br. Med. J. 2 (1974) 705.
24. Rimaiiho, A., Georges, J. L, Vassal, T., Pezzano, M, Richard, Ch., Auzepy, Ph.: Rhombenc6phatites list6rienne avec liquide cephatorachidien initial normal. Presse M6d. 17 (1988) 949-95t. 25. Safran, A. B., Berney, J., Rilliat, B.: L'ophtalmopl6gie internucl6aire dans les enc6phalites infectieuse: observation d'un cas de list6riose. Arch. Suisses Neurol. Neurochir. Psychiatr. 123 (1978) 179. 26. Trautmann, M., Wagner, M., Stoltenburg-Didinger, G., Briickner, O., Bringmann, A.: Rhombencephalitis durch Listeria monocytogenes: Klinische und pathologisch-anatomische Befunde bei einer seltenen Encephalitisform. Nervenarzt 53 (1982) 705, 27. Weinstein, A. J., Schiavone, W. A., Furlan, A. J.: Listeria rhombencephalitis-report of a case. Arch. Neurol. 39 (1982) 514-516. 28. Yersin, B. R., Glauser, M. P., Regli, F.: Infections ~tListeria monocytogenes chez l'adulte. Schweiz. Med. Wschr. 111 (1981) 1596-1602.
29. Zimmer C., Neuen-Jacob, E., M6bius, E., Benn, M., Wechsler, W.: Listeria monocytogenes - Ein ungew6hnlicher Fall einer Listerien-
Encephalitis bei einem gesunden erwachsenen Patienten. Akt. Neurol. 16 (1989) 107-109. 30. Brun-Buisson, C. J., de Gialluly, E , Gherardi, 1L, Otterbein, G.: Fatal nonmeningitic Listeria rhombencephalitis-report of two cases. Arch. Intern. Med. 145 (1985) 1982-1985. 31. Zeman, A., Bamford, J. M., Warlow, C. P , Mitchell, R. G.: Listeria encephalitis with intermittent symptoms and serological diagnosis. I.N.N.P. 51 (1988) 458~59. 32, Kocen, R. S., Mail', W. G. P., Findley, L J, Harvey, P. K. P., Perkin, O.: Brainstem encephalitis caused by Listeria monocytogenes infection. Int. Congress Series No. 472. In: Weinber~ A. N., Heck, A. F. (eds.), Excerpta Medica. Amsterdam-Oxford-New York 1977, p. 269.
44 / 40
33. Pollock, S. S., Pollock, T. M., Harrison, M. J. G.: Infection of the central nervous system by Listeria monocytogenes: a review of 54 adult and juvenile cases. Quarterly J. Med. 211 (1984) 331-340. 34. Hirasawa, H.: Morphologischer Beitrag zur Kenntnis der ListeriaMeningoencephalitis beim Erwachsenen und beim S~iugling. Arch. Psych. Nervenkrkh. 197 (1958) 449-462. 35. Colmant, H. J.: Neuropathologie der Listeriose. Dtsch. Zeitschrift Nervenheilkunde 182 (1961) 492-515. 36. Anonymus: Listeriosis. Br. Med. J. 2 (1971) 477-478. 37. Benazet, F., Sohier, R., Bonjean, M.: Les enc6phalites list6riennes suppur6es. Presse M6d. 65 (1957) 2168-2170. 38. Callea, L, Donati, E., Faggi, L , Sealzani, A., Callea, F.: Pontomedullary encephalitis and basal meningitis due to Listeria monocytogenes: report of a case. Eur. Neurol. 24 (1985) 217-220. 39. Hirsch, F. W., Drexler, H., Meinertz, T., Daschner, F.: Rhombencephalitis by Listeria rnonocytogenes: onset of symptoms two days after perianal injections. Infection 14 (1981) 151. 40. Kennard, C., Howard, A. J., Scholtz, C., Swash, M.: Infection of the brainstem by Listeria monocytogenes. I.N.N.P. 42 (1979) 931-933. 41. Pitner, S. E.: Listerial metencephalitis. South. Med. J. 59 (1966) 564-566. 42. Samson, M., Augustin, P., Verdure, L: A propos de deux cas de m6ningoenc6phalites list6rienne ~t forme bulbo-protub6rantielle. Soc. Fran~. Neurol. 125 (1971) 450-454. 43. Jacobs, J. L., Murray, H. W.: Why is Listeria monocytogenes not a pathogen in the acquired immunodeficiency syndrome? Arch. Intern. Med. 146 (1986) 1299-1300. 44. Mullin, G. E., Sheppell, A. L: Listeria monocytogenes and the acquired immunodeficiency syndrome. Arch. Intern. Med. 147 (1987) 176. 45. Haykal, H.: CT features of early Listeria monocytogenes cerebritis. A.J.N.R. 8 (1987) 279-282. 46. Dee, R. R., Lorber, B.: Brain abscess due to Listeria monocytogenes: Case report and literature review. Rev. Infect. Dis. 8 (1986) 968-977. 47. Davidson, H. D., Steiner, R. E.: MRI in infections of the central nervous system. A.J.N.R. 6 (1985) 499. 48. Marget, W., Seeliger, H. P. R.: Listeria rnonocytogenes infectionstherapeutic possibilities and problems. Infection 16 (Suppl. 2) (1988) 175-177.
Infection 19 (1991) No. 1 © MMV Medizin Verlag GmbH Mtinchen, Miinchen 1991
