J Neurosurg 72:654-659, 1990
Dorsal midbrain encephalitis caused by
P r o p i o n i b a c t e r i u m acHes Report o f two cases
PAUL J. CAMARATA, M.D., ROBERT E. MCGEACHIE, M.D., AND STEPHEN J. HAINES, M.D. Department of Neurosurgery and Division of Neuroradiology, University of Minnesota, Minneapolis, Minnesota ~," A syndrome of dorsal midbrain dysfunction in association with a central nervous system anaerobic diphtheroid infection is described. Two cases of infection with Propionibacterium acnes manifested as shunt malfunctions with a clinical dorsal midbrain syndrome. Magnetic resonance images showed increased signal in the midbrain tectum which has decreased slowly over time. The evidence suggesting that this syndrome represents bacterial midbrain encephalitis is discussed. KEY WORDS brain-stem encephalitis cerebrospinal fluid shunt 9
E
NCEPHALITIS of the brain stem is most frequently presumed to be of viral etiology; L5 however, there are at least 60 reports o f bacterial inflammation of the brain stem with abscess formation. ~6'~7'22'25'4~Streptococcus and Staphylococcus are most c o m m o n l y found in brain-stem abscesses, 19,25while L i s t e r i d ~ and M y c o p l a s m a 2~ have been shown to cause inflammation with and without abscess. We have found only four cases of magnetic resonance imaging of brain-stem encephalitis, bacterial or viral, in the literature. 8,~5,~8 In this report, we present two strikingly similar cases of what we believe to be mesencephalic encephalitis caused by the anaerobic diphtheroid, Propionibacterium aches. Case Reports
Case 1 This 14-year-old boy with headaches was diagnosed as having hydrocephalus in January, 1984, after an ophthalmological examination revealed papilledema, and a computerized t o m o g r a p h y (CT) scan demonstrated massive lateral and third ventricular enlargement. Physical examination was remarkable for a large head and a slightly wide-based gait. A fight frontal ventriculoperitoneal (VP) shunt was placed. Six weeks later, he began to complain of back and neck pain after 654
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jumping on a trampoline, contrary to the advice of his parents and physicians. A C T scan demonstrated collapsed ventricles and bilateral subdural hematomas. The subdural h e m a t o m a s were drained, and the shunt was revised without complications. He underwent two more shunt revisions over the next several months. In November, 1984, the patient presented with a several-day history of decreased level of consciousness, slurred speech, and loss o f upward gaze. His peripheral leukocyte count was 15,800/cu m m with 89% neutrophils. A C T scan showed interval ventricular enlargement, and his shunt was revised. The peritoneal catheter was found to be occluded. A cerebrospinal fluid (CSF) cell count showed 2 white blood cells (WBC's)/cu m m and 50 red blood cells (RBC's)/cu cm. His neurological syndrome persisted, and the peritoneal catheter was again revised 5 days later. He slowly improved, although the paresis of upward gaze persisted. A postoperative shunt tap showed good function and an intracranial pressure (ICP) of 0 m m Hg. A C T scan showed a slight decrease in ventricular size. Two CSF cultures taken during his hospitalization grew P. acHes 4 and 7 days after collection and following the patient's discharge. These growths were initially believed to be contaminants. The patient did well clinically; outpatient examination 1 m o n t h later showed full extraocular moveJ. Neurosurg. / Volume 72~April, 1990
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FIG. 1. Case 1 A: Sagittal intermediate weighted magnetic resonance (MR) image (spin-echo (SE) 1900/ 35 msec) of the midbrain at time of infection. B: Computerized tomography scan without contrast enhancement obtained at the same time as A. C and D: Sagittal (C) and axial (D) MR images (SE 1500/35 reset) 3 months after presentation. E and F: T,-weighted MR images obtained at the 3-year follow-up visit: with gadolinium (SE 850/17 msec) (E) and intermediate-weighted image (SE 700/35 msec) (F).
ments except convergence. The CT studies continued to show decreased ventricular size. Six weeks later the patient presented at the emergency r o o m with increased lethargy, abdominal pain, slurred speech, dilated sluggishly reactive pupils, and a paresis o f convergence and upward gaze. His WBC count was 10,600/cu m m with a normal differential. The shunt was explored, peritoneal insufficiency diagnosed, and the catheter replaced. A CSF cell count showed 1 rnonocyte/cu m m . After 2 days of no improvement, a shunt tap indicated high pressure, and a ventriculostomy was placed to maintain ICP at 5 to 10 m m Hg. Three days after admission, P. acnes began growing from the initial culture and a course o f intravenous cephalothin was instituted. The entire shunt system was externalized at this time, but the patient continued to be minimally responsive with persistent downward deviation of gaze. He had marked hypertonia, resting tremors, diaphoresis, and decerebrate posturing. Magnetic resonance (MR) images obtained at this time showed an area J. Neurosurg. / Volume 72/April, 1990
of increased intensity on first-echo (Fig. I A) and T2weighted images in an expanded midbrain tectum. No lesion was seen on a CT scan without contrast enhancement, although retrospective review suggests an equivocal increase in density in the tectal area (Fig. 1B). After five CSF cultures taken 24 hours apart were negative for at least 72 hours, a new VP shunt was placed. He received antibiotics for a total of 17 days. The patient demonstrated very slow but steady neurological improvement. Subsequently, daily cultures up to the day prior to surgery grew out P. acnes. His shunt malfunctioned 3 m o n t h s later and was revised to a ventriculoatial (VA) shunt. At this time, M R imaging showed little change in the lesion (Fig. IC and D). Over the ensuing months he regained full extraocular m o v e m e n t and began attending classes at this university. Repeat M R images 3 years after initial diagnosis demonstrated decreased deformation in the tectal area but no enhancem e n t with gadolinium (Fig. 1E) and a slightly increased signal in the midbrain on first-echo images (Fig. 1F). 655
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FIG. 2. Case 2. A and B: Computerized tomography scans without (A) and with (B) contrast enhancement at time of presentation. C and D: Intermediate-weighted magnetic resonance images (spin-echo (SE) 1500/ 35 msec) 1 month after presentation at the time of maximum debilitation. E and F: Magnetic resonance images obtained 18 months after initial presentation: SE 500/16 msec (E) and SE 2700/35 msec (F). G and H: Magnetic resonance images obtained at the 3-year follow-up visit: SE 850/17 msec (G) and SE 3300/24 msec (H).
Case 2
This 19-year-old m a n was referred to the University of Minnesota in March, 1985, after a series of shunt malfunctions. He was initially diagnosed in July, 1981, as having hydrocephalus, presumed due to aqueductal stenosis. He did well following placement of a fight parietal VP shunt until January, 1985, when he presented with symptoms o f shunt malfunction including somnolence, headache, and confusion. He also had paresis of upward gaze. The ventricular catheter was found to be obstructed by choroid plexus and was revised. Cerebrospinal fluid studies including cultures were unremarkable. Ten days later, his upward gaze paresis remained and he again became m o r e lethargic. A C T scan indicated large lateral and third ventricles, and the shunt was again revised. Examination of CSF obtained at the time of surgery again showed it to be sterile. A left-sided shunt was placed 1 m o n t h later when the patient's gait and alertness deteriorated. A C T scan again showed large ventricles. His upward gaze paresis persisted after surgery, although C T scans showed decreased ventriculomegaly. Four weeks later his complaints included 2 weeks o f abdominal pain, persistent upward gaze paralysis, headache, nausea, lethargy, and fever. A CT scan of the head demonstrated massive ventriculomegaly; an abdominal CT scan was unre656
markable. His admission WBC count was 16,500/cu m m with a left shift. After blood samples were drawn for culture, intravenous tobramycin and cephalothin were instituted. His shunt was urgently revised and, when no clinical i m p r o v e m e n t was seen, a ventriculost o m y was placed without clinical change. The CSF contained 13 WBC's (8% neutrophils) and 550 RBC's/ cu cm. It was at this point that he was transferred to our care. The patient was obtunded with no speech, and he followed c o m m a n d s intermittently. His pupils were sluggishly reactive, and he had no upgaze on oculovestibular testing. Between episodes of decerebrate posturing, he would m o v e his extremities purposefully to pain. He had a peripheral WBC count of 15,400/cu m m with a marked left shift. Electrolytes were within normal limits. A CSF cell count showed 149 WBC's/cu cm with 61% neutrophils. A C T scan showed enlarged ventricles and a radionuclide shunt study showed a functioning shunt on the left. Ventricular drainage was maintained to keep ICP below 5 m m Hg for 4 days, yet the patient showed no clinical i m p r o v e m e n t and his ventricles did not decrease in size. At this point, a CSF culture obtained 2 days prior to transfer began growing out diphtheroids. Both shunts were externalized. Five days later, when several CSF cultures had been reported negative after 72 hours, J. Neurosurg. / Volume 7 2 / A p r i l 1990
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a new shunt was placed and the old systems were removed. Subsequently, all preoperative cultures including one obtained on the day of surgery grew diphtheroids. No postoperative cultures were positive. The patient continued to receive cephalothin, and serial CT showed a steady decrease in size of the ventricles. Clinically, he remained unarousable with a downward deviated gaze. A C T scan showed a swollen quadrigeminal plate which did not enhance with contrast material (Fig. 2A and B). An M R image showed an increased signal in the expanded tectal plate, which was thought might represent a glioma or inflammation (Fig. 2C and D). Electroencephalography showed diffuse slowing, and CSF studies sent for myelin basic protein and counter-immunoelectrophoresis were normal. When CT scans again demonstrated increased ventricular size, the shunt was revised to a VA shunt. Over the next several weeks the patient slowly improved to the point where he could follow one-step commands and verbalize two-word phrases. He was markedly bradykinetic and hypertonic, with tremors and a persistent upward gaze paresis. Six months later his only deficit was mild fine m o t o r incoordination. He had normal extraocular m o v e m e n t s and convergence. Multiple modality evoked responses were normal. Neuropsychometric testing revealed above-average intelligence, reduced attentional capacity, and a slight recent m e m o r y disorder. Overall, the results were suggestive of "possible dysfunction in the midbrain arousal structures." The patient continued to improve and was able to return to college classes. An 18-month follow-up MR image demonstrated a persistent increased signal in the midbrain with enlargement of the quadrigeminal plate (Fig. 2E and F). Studies at the 3-year follow-up review continued to show an abnormal signal in this area, although decreased in intensity (Fig. 2G and H). Discussion P r o p i o n i b a c t e r i u m a c n e s are Gram-positive, anaer-
obic, non-motile rods found in abundance on human skin. 24 They are often referred to as diphtheroids because they are technically part of the C o r y n e b a c t e r i u m genus, and because of their similarity to C. diphtheriae. These bacteria, thought to play a part in the etiology of c o m m o n acne, have been isolated from up to 100% of s u b j e c t s . 24 They are particularly prevalent in areas containing a large n u m b e r of sebaceous follicles, namely the forehead, scalp, presternal area, and upper back. The unsaturated fatty acids secreted onto the skin provide an ideal environment for these strict anaerobes. The infectious spectrum of P. a c n e s is well documented in the neurological literature. It has been recognized as a c o m m o n cause of shunt infection, colonization, and ultimately malfunction. It has been shown to cause a disabling chronic meningitis in previously healthy patients without previous s u r g e r y . 14,39 It has also been implicated in acute, fulminant meningitis, 32 postoperative wound infections, 7'4~subdural fluid infecJ. Neurosurg. / Volume 7 2 / A p r i l , 1990
tion, 6 intracerebral a b s c e s s , 29 and i m m u n e complexmediated shunt nephritis. 13 These are the first cases suggesting a role of P. a c n e s in the pathogenesis of a midbrain inflammatory process. P. a c n e s has been incriminated in the pathogenesis of CSF shunt infections?.11-13.27.34.35 The actual n u m b e r of infections caused by these bacteria is probably greater than reported for several reasons. First, the organism often goes undetected in routine aerobic CSF cultures because it is a fastidious anaerobe. 35 Unless specimens are routinely sent for separate culture and transported in anaerobic media, they will often fail to grow out. Even then, it is c o m m o n for growth to be delayed as long as 1 week. 7 Second, because the organism is so prevalent on the skin, when it grows in small a m o u n t s on routine culture m e d i u m it is frequently reported as a contaminant. 2~ Third, the clinical central nervous system (CNS) infection produced by P. a c n e s can range from an a s y m p t o m a t i c colonization to fulminant meningitis. The CSF cell count has been reported to show mild to p r o m i n e n t leukocytosis. 7,11,27,35 These two cases appear to be typical of other cases of P. a c n e s infection both from our institution and from the literature in several respects. The isolation and recognition of P. a c n e s as a pathogen in each of these examples were delayed by late growth and by labeling of the culture result as a "contaminant." Several shunt system malfunctions and revisions were required before the problem was recognized and finally brought under control. These cases are unique in several respects. The slow development and persistence of upward gaze paresis in combination with pupillary abnormalities and obtundation in these patients seems to point to the midbrain as the site of pathology. The appearance of M R images of an area of increased signal in the midbrain rectum of each patient would seem to confirm this. Increased ICP was initially considered to be responsible for the Parinaud's syndrome. However, the syndrome persisted despite normalization of ICP. In both of these patients the initial diagnosis was hydrocephalus secondary to aqueductal stenosis. Both cases were brought to medical attention in mid to late adolescence, a time when P. a c n e s skin colonization is at its peak. 24 The CSF cell count was for the most part unremarkable despite the repeated presence of the diphtheroid bacilli in cultures. This characteristic of a slow, indolent infection of low virulence is reflected in the literature and can account for the pattern of repeated shunt malfunction/obstruction in the absence of an overt, purulent infectious process. The location o f abnormalities seen on M R imaging corresponds well to the clinical syndrome. Although a neoplastic process, such as a glioma, was entertained as a possible diagnosis, the likelihood that this is the case is small given the recovery of each patient following a course of antibiotics, and the i m p r o v e m e n t on followup M R images. We believe that the clinical and imaging evidence suggests a structural dorsal midbrain lesion 657
P. J. Camarata, R. E. McGeachie, and S. J. Haines occurring in conjunction with documented CSF infection, and is most consistent with midbrain encephalitis caused by P. aches. In her classic treatise, Russell 3~demonstrated luminal areas denuded of ependyma in cases of aqueductal stenosis due to gliosis. This gliosis in the aqueduct of Sylvius is more frequently found in non-myelomeningocele hydrocephalic brains than in normal brains. 33 The ependymal lining of the aqueduct in these brains has been shown to be often defective with islands of ependyma buried beneath the lumen. Experimental evidence using the congenital murine hydrocephalus model showed similar denuded areas in the aqueduct, although this was not extensive. 26 These luminal defects may represent an avenue by which bacteria would gain easier access to midbrain parenchyma. Brain-stem encephalitis is a rare disorder and can present with a variety of symptoms including cranialnerve and bulbar dysfunction and obtundation. 1,2,38 In the classic description, Bickerstaff5 reviewed eight cases with ophthalmoplegia, other cranial nerve palsies, and ataxia. The clinical picture progressed from nonspecific prodromal symptoms to neurological signs indicative of brain-stem pathology. Patients became severely lethargic and disabled neurologically; however, they generally recovered over the course of several weeks to months. Interestingly, several of his cases developed a transient Parkinson-like s y m p t o m complex (resting tremor, masked facies, bradykinesia) during the course of their recovery. Since that report, other similar cases have been reported, 4.31,42 most describing a viral-type prodromal symptomatology. Bacterial invasion of the brain stem is less frequently reported. L i s t e r i a m o n o c y t o g e n e s appears to have a particular predilection for the brain stem, being implicated in several cases of abscess or encephalitis, j~ Although other bacteria have been reported to cause brain-stem abscess, low-grade chronic inflammation has been almost universally ascribed to infection with virus. As P. a c n e s has been described as a pathogen with low virulence and has been shown to be responsible for subclinical and chronic CNS infections, it seems likely that it could be implicated in brain-stern encephalitis. There are only four reports o f M R imaging characteristics in brain-stem encephalitis, 8,15,18 and several cases with normal M R studies. 8,28 However, none of these cases presented specifically with the dorsal midbrain syndrome.* There are two reports in the literature o f Fisher's syndrome (the specific symptom complex including ophthalmoplegia, ataxia, and hyporeflexia) with a tegmental lesion seen on CT scanning. 9,36 The M R images of our two patients showed areas of increased signal on intermediate and T2-weighted images * Since these two cases were reported, we have seen a third patient with virtually identical symptomatology, including multiple shunt malfunctions and infection with P. aches, but without the observed changes of MR imaging. 658
very similar to those reported in the literature. None of the cases reported previously has shown images obtained years after the lesion was diagnosed. Our patients would suggest that the lesion will lessen in signal intensity over time, but may not completely disappear. It might be argued that the present cases represent typical Bickerstaff encephalitis or atypical cases of Fisher's syndrome, in which complete recovery is most often the case and the cause is probably viral. If that were so, the hydrocephalus and shunt infections caused by P. a c h e s would have occurred simultaneously. Because of the extreme rarity of the entity itself, and the coincidental association in these cases with shunt infections caused by P. aches, we believe this scenario to be unlikely. In summary, we believe that untreated CSF infections with P. a c h e s can progress to parenchymal involvement producing structural lesions visible on M R imaging that cause virulent, life-threatening disease. P r o p i o n i b a c t e r i u m a c h e s isolated from the CSF, especially in association with a shunt, must be treated seriously and not viewed as a contaminant without exhaustive investigation. References
1. A1-Din AN, Anderson M, Bickerstaff ER, et al: Brainstem encephalitis and the syndrome of Miller Fisher. Brain 105:481-495, 1982 2. Baloh RW, Furman JM, Yee RD: Dorsal midbrain syndrome: clinical and oculographic findings. Neurology 35: 54-60, 1985 3. Beeler BA, Crowder JG, Smith JW, et al: Propionibacterium aches: pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulonephritis. Am J Med 61:935-938, 1976 4. Bhoola RL, Patel PL, Cosnett JE, et al: Brainstem encephalitis or the Miller Fisher syndrome - - a variant of acute idiopathic polyneuropathy. S Aft Med J 64: 1035-1036, 1983 5. Bickerstaff ER: Brain-stem encephalitis: further observations on a grave syndrome with benign prognosis. Br Med J 1:1384-1387, 1957 6. Cohle SD, Hinds D, Yawn DH: Propionibacterium acnes infection following subdural tap. Am J Clin Pathol 75:430-431, 1981 7. Collignon PJ, Munro R, Sorrel TC: Propionibacterium aches infection in neurosurgical patients. Med J Aust 145:408-410, 1986 8. Davidson HD, Steiner RE: Magnetic resonance imaging in infections of the central nervous system. AJNR 6: 499-504, 1985 9. Derakhshan I, Lotfi J, Kaukfman B: Ophthalmoplegia, ataxia and hyporeflexia (Fisher's syndrome) with a midbrain lesion demonstrated by CT scanning. Eur Neurol 18:361-366, 1979 10. Duffy PE, Sassin JF, Summers DS, et al: Rhombencephalitis due to Listeria monocytogenes. Neurology 14: 1067-1072, 1964 11. Everett ED, Eickhoff TC, Simon RH: Cerebrospinal fluid shunt infections with anaerobic diphtheroids. (Propionibacterium species.) J Neurosurg 44:580-584, 1976 12. Forward KR, Fewer D, Stiver HG: Cerebrospinal fluid shunt infections. A review of 35 infections in 32 patients. J. Neurosurg. / Volume 7 2 / A p r i l , 1990
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J Neurosurg 59:389-394, 1983 13. Frank JA, Friedman HS, Davidson DM, et at: Propionibacterium shunt nephritis in two adolescents with medulloblastoma. Cancer 52:330-333, 1983 14. French RS, Ziter FA, Spruance SL, et at: Chronic meningitis caused by Propionibacterium aches. A potentially important clinical entity. Neurology 24:624-628, 1974 15. Furman JM, Brownstone PK, Baloh RW: Atypical brainstem encephalitis: magnetic resonance imaging and oculographic features. Neurology 35:438-440, 1985 16. Gaida JB: Pontile abscess. Arch Otolaryngol 30:93-95, 1939 17. Harvey FH, Carlow T J: Brainstem abscess and syndrome of acute tegmental encephalitis. Ann Neurol 7:371-376, 1980 18. Hosoda K, Tamaki N, Masumura M, et at: Magnetic resonance images of brain-stem encephalitis. Case report. J Neurosurg 66:283-285, 1987 19. Hulme A: Suppurative lesions of the brainstem. J Neurol Neurosurg Psychiatry 24:291-293, 1961 20. Jachuck SJ, Gardner-Thorpe C, Clark F, et al: A brainstem syndrome associated with Mycoplasma pneumoniae infection. Postgrad Med J 51:475-477, 1975 21. Kaplan K, Weinstein L: Diphtheroid infections in man. Ann Intern Med 70:919-929, 1979 22. Kashiwagi S, Abiko S, Aoki H: Brainstem abscess. Surg Neurol 28:63-66, 1987 23. Kennard C, Howard AJ, Scholtz C, et al: Infection of the brainstem by Listeria monocytogenes. J Neurol Neurosurg Psychiatry 42:931-933, 1979 24. Noble WC: Microbiology of Human Skin. London: Lloyd-Luke Medical, 1981, pp 115-151,366-375 25. Parker RL, Collins GH: Intramedullary abscess of the brain stem and spinal cord. South Med J 63:493-497, 1970 26. Raimondi A J, Clark SJ, McLone DG: Pathogenesis of aqueductal occlusion in congenital murine hydrocephalus. J Neurosurg 45:66-77, 1976 27. Rekate HL, Ruch T, Nulsen FE: Diphtheroid infections of cerebrospinal fluid shunts. The changing pattern of shunt infection in Cleveland. J Neurosurg 52:553-556, 1980 28. Ropper AH: Three patients with Fisher's syndrome and normal MRI. Neurology 38:1630-1631, 1988 29. Rosenblum ML, Hoff JT, Norman D, et al: Nonoperative treatment of brain abscesses in selected high-risk patients. J Neurosurg 52:217-225, 1980
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30. Russell DS: Observations on the Pathology of Hydrocephalus. Medical Research Council Special Report Series 265. London: H M Stationery Office, 1949 31. Sandyk R, Brennan MJW: BickerstalTs brainstem encephalitis in Johannesburg. S Afr Med J 64:179-180, 1983 32. Schlesinger J J, Ross AL: Propionibacterium aches meningitis in a previously normal adult. Arch Intern Med 137:921-923, 1977 33. Shellshear 1, Emery JL: Gliosis and aqueductule formation in the aqueduct of Sylvius. Dev Med Child Neurol 18 (Suppl 37):22-28, 1976 34. Skinner PR, Taylor A J, Coakham H: Propionibacteria as a cause of shunt and postneurosurgicat infections. J Clin Pathol 31:1085-1090, 1978 35. Strand CL, Dubois RE: Propionibacterium acnes central nervous system shunt infection. Am J Clin Pathol 75: 743-746, 1981 36. Tachi N, Tsuzuki Y, Minami R: A case of brainstem encephalitis with CT scan abnormality mimicking Fisher syndrome. Brain Dev 8:538-541, 1986 37. Trautmann M, Wagner J, Chahin M, et at: Listeria meningitis: report of 10 recent cases and review of current therapeutic recommendations. J Infect 10:107-114, 1985 38. UenoT, TakahataN: Chronic brainstem encephalitis with mental symptoms and ataxia. J Neurol Neurosurg Psychiatry 41:516-524, 1978 39. Ueunten D, Tobias J, Sochat M, et at: An unusual cause of bacterial meningitis in the elderly: Propionibacterium acnes. Arch Neurol 40:388-389, 1983 40. VanEk B, Bakker FP, van Dulken H, et al: Infections after craniotomy: a retrospective study. J Infect 12: 105-109, 1986 41. VanGilder JC, Allen WE III, Lesser RA: Pontine abscess: survival following surgical drainage. Case report. J Neurosurg 40:386-390, 1974 42. Waxman SG, Sabin TD, Embree SJ: Subacute brainstem encephalitis. J Neurol Neurosurg Psychiatry 37: 811-816, 1974
Manuscript received July 10, 1989. Address reprint requests to: Paul J. Camarata, M.D., Department of Neurosurgery, University of Minnesota, Box 96 UMHC, B590 Mayo Memorial Building, 420 Delaware Street S.E., Minneapolis, Minnesota 55455.
659
Dorsal midbrain encephalitis caused by
P r o p i o n i b a c t e r i u m acHes Report o f two cases
PAUL J. CAMARATA, M.D., ROBERT E. MCGEACHIE, M.D., AND STEPHEN J. HAINES, M.D. Department of Neurosurgery and Division of Neuroradiology, University of Minnesota, Minneapolis, Minnesota ~," A syndrome of dorsal midbrain dysfunction in association with a central nervous system anaerobic diphtheroid infection is described. Two cases of infection with Propionibacterium acnes manifested as shunt malfunctions with a clinical dorsal midbrain syndrome. Magnetic resonance images showed increased signal in the midbrain tectum which has decreased slowly over time. The evidence suggesting that this syndrome represents bacterial midbrain encephalitis is discussed. KEY WORDS brain-stem encephalitis cerebrospinal fluid shunt 9
E
NCEPHALITIS of the brain stem is most frequently presumed to be of viral etiology; L5 however, there are at least 60 reports o f bacterial inflammation of the brain stem with abscess formation. ~6'~7'22'25'4~Streptococcus and Staphylococcus are most c o m m o n l y found in brain-stem abscesses, 19,25while L i s t e r i d ~ and M y c o p l a s m a 2~ have been shown to cause inflammation with and without abscess. We have found only four cases of magnetic resonance imaging of brain-stem encephalitis, bacterial or viral, in the literature. 8,~5,~8 In this report, we present two strikingly similar cases of what we believe to be mesencephalic encephalitis caused by the anaerobic diphtheroid, Propionibacterium aches. Case Reports
Case 1 This 14-year-old boy with headaches was diagnosed as having hydrocephalus in January, 1984, after an ophthalmological examination revealed papilledema, and a computerized t o m o g r a p h y (CT) scan demonstrated massive lateral and third ventricular enlargement. Physical examination was remarkable for a large head and a slightly wide-based gait. A fight frontal ventriculoperitoneal (VP) shunt was placed. Six weeks later, he began to complain of back and neck pain after 654
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jumping on a trampoline, contrary to the advice of his parents and physicians. A C T scan demonstrated collapsed ventricles and bilateral subdural hematomas. The subdural h e m a t o m a s were drained, and the shunt was revised without complications. He underwent two more shunt revisions over the next several months. In November, 1984, the patient presented with a several-day history of decreased level of consciousness, slurred speech, and loss o f upward gaze. His peripheral leukocyte count was 15,800/cu m m with 89% neutrophils. A C T scan showed interval ventricular enlargement, and his shunt was revised. The peritoneal catheter was found to be occluded. A cerebrospinal fluid (CSF) cell count showed 2 white blood cells (WBC's)/cu m m and 50 red blood cells (RBC's)/cu cm. His neurological syndrome persisted, and the peritoneal catheter was again revised 5 days later. He slowly improved, although the paresis of upward gaze persisted. A postoperative shunt tap showed good function and an intracranial pressure (ICP) of 0 m m Hg. A C T scan showed a slight decrease in ventricular size. Two CSF cultures taken during his hospitalization grew P. acHes 4 and 7 days after collection and following the patient's discharge. These growths were initially believed to be contaminants. The patient did well clinically; outpatient examination 1 m o n t h later showed full extraocular moveJ. Neurosurg. / Volume 72~April, 1990
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FIG. 1. Case 1 A: Sagittal intermediate weighted magnetic resonance (MR) image (spin-echo (SE) 1900/ 35 msec) of the midbrain at time of infection. B: Computerized tomography scan without contrast enhancement obtained at the same time as A. C and D: Sagittal (C) and axial (D) MR images (SE 1500/35 reset) 3 months after presentation. E and F: T,-weighted MR images obtained at the 3-year follow-up visit: with gadolinium (SE 850/17 msec) (E) and intermediate-weighted image (SE 700/35 msec) (F).
ments except convergence. The CT studies continued to show decreased ventricular size. Six weeks later the patient presented at the emergency r o o m with increased lethargy, abdominal pain, slurred speech, dilated sluggishly reactive pupils, and a paresis o f convergence and upward gaze. His WBC count was 10,600/cu m m with a normal differential. The shunt was explored, peritoneal insufficiency diagnosed, and the catheter replaced. A CSF cell count showed 1 rnonocyte/cu m m . After 2 days of no improvement, a shunt tap indicated high pressure, and a ventriculostomy was placed to maintain ICP at 5 to 10 m m Hg. Three days after admission, P. acnes began growing from the initial culture and a course o f intravenous cephalothin was instituted. The entire shunt system was externalized at this time, but the patient continued to be minimally responsive with persistent downward deviation of gaze. He had marked hypertonia, resting tremors, diaphoresis, and decerebrate posturing. Magnetic resonance (MR) images obtained at this time showed an area J. Neurosurg. / Volume 72/April, 1990
of increased intensity on first-echo (Fig. I A) and T2weighted images in an expanded midbrain tectum. No lesion was seen on a CT scan without contrast enhancement, although retrospective review suggests an equivocal increase in density in the tectal area (Fig. 1B). After five CSF cultures taken 24 hours apart were negative for at least 72 hours, a new VP shunt was placed. He received antibiotics for a total of 17 days. The patient demonstrated very slow but steady neurological improvement. Subsequently, daily cultures up to the day prior to surgery grew out P. acnes. His shunt malfunctioned 3 m o n t h s later and was revised to a ventriculoatial (VA) shunt. At this time, M R imaging showed little change in the lesion (Fig. IC and D). Over the ensuing months he regained full extraocular m o v e m e n t and began attending classes at this university. Repeat M R images 3 years after initial diagnosis demonstrated decreased deformation in the tectal area but no enhancem e n t with gadolinium (Fig. 1E) and a slightly increased signal in the midbrain on first-echo images (Fig. 1F). 655
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FIG. 2. Case 2. A and B: Computerized tomography scans without (A) and with (B) contrast enhancement at time of presentation. C and D: Intermediate-weighted magnetic resonance images (spin-echo (SE) 1500/ 35 msec) 1 month after presentation at the time of maximum debilitation. E and F: Magnetic resonance images obtained 18 months after initial presentation: SE 500/16 msec (E) and SE 2700/35 msec (F). G and H: Magnetic resonance images obtained at the 3-year follow-up visit: SE 850/17 msec (G) and SE 3300/24 msec (H).
Case 2
This 19-year-old m a n was referred to the University of Minnesota in March, 1985, after a series of shunt malfunctions. He was initially diagnosed in July, 1981, as having hydrocephalus, presumed due to aqueductal stenosis. He did well following placement of a fight parietal VP shunt until January, 1985, when he presented with symptoms o f shunt malfunction including somnolence, headache, and confusion. He also had paresis of upward gaze. The ventricular catheter was found to be obstructed by choroid plexus and was revised. Cerebrospinal fluid studies including cultures were unremarkable. Ten days later, his upward gaze paresis remained and he again became m o r e lethargic. A C T scan indicated large lateral and third ventricles, and the shunt was again revised. Examination of CSF obtained at the time of surgery again showed it to be sterile. A left-sided shunt was placed 1 m o n t h later when the patient's gait and alertness deteriorated. A C T scan again showed large ventricles. His upward gaze paresis persisted after surgery, although C T scans showed decreased ventriculomegaly. Four weeks later his complaints included 2 weeks o f abdominal pain, persistent upward gaze paralysis, headache, nausea, lethargy, and fever. A CT scan of the head demonstrated massive ventriculomegaly; an abdominal CT scan was unre656
markable. His admission WBC count was 16,500/cu m m with a left shift. After blood samples were drawn for culture, intravenous tobramycin and cephalothin were instituted. His shunt was urgently revised and, when no clinical i m p r o v e m e n t was seen, a ventriculost o m y was placed without clinical change. The CSF contained 13 WBC's (8% neutrophils) and 550 RBC's/ cu cm. It was at this point that he was transferred to our care. The patient was obtunded with no speech, and he followed c o m m a n d s intermittently. His pupils were sluggishly reactive, and he had no upgaze on oculovestibular testing. Between episodes of decerebrate posturing, he would m o v e his extremities purposefully to pain. He had a peripheral WBC count of 15,400/cu m m with a marked left shift. Electrolytes were within normal limits. A CSF cell count showed 149 WBC's/cu cm with 61% neutrophils. A C T scan showed enlarged ventricles and a radionuclide shunt study showed a functioning shunt on the left. Ventricular drainage was maintained to keep ICP below 5 m m Hg for 4 days, yet the patient showed no clinical i m p r o v e m e n t and his ventricles did not decrease in size. At this point, a CSF culture obtained 2 days prior to transfer began growing out diphtheroids. Both shunts were externalized. Five days later, when several CSF cultures had been reported negative after 72 hours, J. Neurosurg. / Volume 7 2 / A p r i l 1990
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a new shunt was placed and the old systems were removed. Subsequently, all preoperative cultures including one obtained on the day of surgery grew diphtheroids. No postoperative cultures were positive. The patient continued to receive cephalothin, and serial CT showed a steady decrease in size of the ventricles. Clinically, he remained unarousable with a downward deviated gaze. A C T scan showed a swollen quadrigeminal plate which did not enhance with contrast material (Fig. 2A and B). An M R image showed an increased signal in the expanded tectal plate, which was thought might represent a glioma or inflammation (Fig. 2C and D). Electroencephalography showed diffuse slowing, and CSF studies sent for myelin basic protein and counter-immunoelectrophoresis were normal. When CT scans again demonstrated increased ventricular size, the shunt was revised to a VA shunt. Over the next several weeks the patient slowly improved to the point where he could follow one-step commands and verbalize two-word phrases. He was markedly bradykinetic and hypertonic, with tremors and a persistent upward gaze paresis. Six months later his only deficit was mild fine m o t o r incoordination. He had normal extraocular m o v e m e n t s and convergence. Multiple modality evoked responses were normal. Neuropsychometric testing revealed above-average intelligence, reduced attentional capacity, and a slight recent m e m o r y disorder. Overall, the results were suggestive of "possible dysfunction in the midbrain arousal structures." The patient continued to improve and was able to return to college classes. An 18-month follow-up MR image demonstrated a persistent increased signal in the midbrain with enlargement of the quadrigeminal plate (Fig. 2E and F). Studies at the 3-year follow-up review continued to show an abnormal signal in this area, although decreased in intensity (Fig. 2G and H). Discussion P r o p i o n i b a c t e r i u m a c n e s are Gram-positive, anaer-
obic, non-motile rods found in abundance on human skin. 24 They are often referred to as diphtheroids because they are technically part of the C o r y n e b a c t e r i u m genus, and because of their similarity to C. diphtheriae. These bacteria, thought to play a part in the etiology of c o m m o n acne, have been isolated from up to 100% of s u b j e c t s . 24 They are particularly prevalent in areas containing a large n u m b e r of sebaceous follicles, namely the forehead, scalp, presternal area, and upper back. The unsaturated fatty acids secreted onto the skin provide an ideal environment for these strict anaerobes. The infectious spectrum of P. a c n e s is well documented in the neurological literature. It has been recognized as a c o m m o n cause of shunt infection, colonization, and ultimately malfunction. It has been shown to cause a disabling chronic meningitis in previously healthy patients without previous s u r g e r y . 14,39 It has also been implicated in acute, fulminant meningitis, 32 postoperative wound infections, 7'4~subdural fluid infecJ. Neurosurg. / Volume 7 2 / A p r i l , 1990
tion, 6 intracerebral a b s c e s s , 29 and i m m u n e complexmediated shunt nephritis. 13 These are the first cases suggesting a role of P. a c n e s in the pathogenesis of a midbrain inflammatory process. P. a c n e s has been incriminated in the pathogenesis of CSF shunt infections?.11-13.27.34.35 The actual n u m b e r of infections caused by these bacteria is probably greater than reported for several reasons. First, the organism often goes undetected in routine aerobic CSF cultures because it is a fastidious anaerobe. 35 Unless specimens are routinely sent for separate culture and transported in anaerobic media, they will often fail to grow out. Even then, it is c o m m o n for growth to be delayed as long as 1 week. 7 Second, because the organism is so prevalent on the skin, when it grows in small a m o u n t s on routine culture m e d i u m it is frequently reported as a contaminant. 2~ Third, the clinical central nervous system (CNS) infection produced by P. a c n e s can range from an a s y m p t o m a t i c colonization to fulminant meningitis. The CSF cell count has been reported to show mild to p r o m i n e n t leukocytosis. 7,11,27,35 These two cases appear to be typical of other cases of P. a c n e s infection both from our institution and from the literature in several respects. The isolation and recognition of P. a c n e s as a pathogen in each of these examples were delayed by late growth and by labeling of the culture result as a "contaminant." Several shunt system malfunctions and revisions were required before the problem was recognized and finally brought under control. These cases are unique in several respects. The slow development and persistence of upward gaze paresis in combination with pupillary abnormalities and obtundation in these patients seems to point to the midbrain as the site of pathology. The appearance of M R images of an area of increased signal in the midbrain rectum of each patient would seem to confirm this. Increased ICP was initially considered to be responsible for the Parinaud's syndrome. However, the syndrome persisted despite normalization of ICP. In both of these patients the initial diagnosis was hydrocephalus secondary to aqueductal stenosis. Both cases were brought to medical attention in mid to late adolescence, a time when P. a c n e s skin colonization is at its peak. 24 The CSF cell count was for the most part unremarkable despite the repeated presence of the diphtheroid bacilli in cultures. This characteristic of a slow, indolent infection of low virulence is reflected in the literature and can account for the pattern of repeated shunt malfunction/obstruction in the absence of an overt, purulent infectious process. The location o f abnormalities seen on M R imaging corresponds well to the clinical syndrome. Although a neoplastic process, such as a glioma, was entertained as a possible diagnosis, the likelihood that this is the case is small given the recovery of each patient following a course of antibiotics, and the i m p r o v e m e n t on followup M R images. We believe that the clinical and imaging evidence suggests a structural dorsal midbrain lesion 657
P. J. Camarata, R. E. McGeachie, and S. J. Haines occurring in conjunction with documented CSF infection, and is most consistent with midbrain encephalitis caused by P. aches. In her classic treatise, Russell 3~demonstrated luminal areas denuded of ependyma in cases of aqueductal stenosis due to gliosis. This gliosis in the aqueduct of Sylvius is more frequently found in non-myelomeningocele hydrocephalic brains than in normal brains. 33 The ependymal lining of the aqueduct in these brains has been shown to be often defective with islands of ependyma buried beneath the lumen. Experimental evidence using the congenital murine hydrocephalus model showed similar denuded areas in the aqueduct, although this was not extensive. 26 These luminal defects may represent an avenue by which bacteria would gain easier access to midbrain parenchyma. Brain-stem encephalitis is a rare disorder and can present with a variety of symptoms including cranialnerve and bulbar dysfunction and obtundation. 1,2,38 In the classic description, Bickerstaff5 reviewed eight cases with ophthalmoplegia, other cranial nerve palsies, and ataxia. The clinical picture progressed from nonspecific prodromal symptoms to neurological signs indicative of brain-stem pathology. Patients became severely lethargic and disabled neurologically; however, they generally recovered over the course of several weeks to months. Interestingly, several of his cases developed a transient Parkinson-like s y m p t o m complex (resting tremor, masked facies, bradykinesia) during the course of their recovery. Since that report, other similar cases have been reported, 4.31,42 most describing a viral-type prodromal symptomatology. Bacterial invasion of the brain stem is less frequently reported. L i s t e r i a m o n o c y t o g e n e s appears to have a particular predilection for the brain stem, being implicated in several cases of abscess or encephalitis, j~ Although other bacteria have been reported to cause brain-stem abscess, low-grade chronic inflammation has been almost universally ascribed to infection with virus. As P. a c n e s has been described as a pathogen with low virulence and has been shown to be responsible for subclinical and chronic CNS infections, it seems likely that it could be implicated in brain-stern encephalitis. There are only four reports o f M R imaging characteristics in brain-stem encephalitis, 8,15,18 and several cases with normal M R studies. 8,28 However, none of these cases presented specifically with the dorsal midbrain syndrome.* There are two reports in the literature o f Fisher's syndrome (the specific symptom complex including ophthalmoplegia, ataxia, and hyporeflexia) with a tegmental lesion seen on CT scanning. 9,36 The M R images of our two patients showed areas of increased signal on intermediate and T2-weighted images * Since these two cases were reported, we have seen a third patient with virtually identical symptomatology, including multiple shunt malfunctions and infection with P. aches, but without the observed changes of MR imaging. 658
very similar to those reported in the literature. None of the cases reported previously has shown images obtained years after the lesion was diagnosed. Our patients would suggest that the lesion will lessen in signal intensity over time, but may not completely disappear. It might be argued that the present cases represent typical Bickerstaff encephalitis or atypical cases of Fisher's syndrome, in which complete recovery is most often the case and the cause is probably viral. If that were so, the hydrocephalus and shunt infections caused by P. a c h e s would have occurred simultaneously. Because of the extreme rarity of the entity itself, and the coincidental association in these cases with shunt infections caused by P. aches, we believe this scenario to be unlikely. In summary, we believe that untreated CSF infections with P. a c h e s can progress to parenchymal involvement producing structural lesions visible on M R imaging that cause virulent, life-threatening disease. P r o p i o n i b a c t e r i u m a c h e s isolated from the CSF, especially in association with a shunt, must be treated seriously and not viewed as a contaminant without exhaustive investigation. References
1. A1-Din AN, Anderson M, Bickerstaff ER, et al: Brainstem encephalitis and the syndrome of Miller Fisher. Brain 105:481-495, 1982 2. Baloh RW, Furman JM, Yee RD: Dorsal midbrain syndrome: clinical and oculographic findings. Neurology 35: 54-60, 1985 3. Beeler BA, Crowder JG, Smith JW, et al: Propionibacterium aches: pathogen in central nervous system shunt infection. Report of three cases including immune complex glomerulonephritis. Am J Med 61:935-938, 1976 4. Bhoola RL, Patel PL, Cosnett JE, et al: Brainstem encephalitis or the Miller Fisher syndrome - - a variant of acute idiopathic polyneuropathy. S Aft Med J 64: 1035-1036, 1983 5. Bickerstaff ER: Brain-stem encephalitis: further observations on a grave syndrome with benign prognosis. Br Med J 1:1384-1387, 1957 6. Cohle SD, Hinds D, Yawn DH: Propionibacterium acnes infection following subdural tap. Am J Clin Pathol 75:430-431, 1981 7. Collignon PJ, Munro R, Sorrel TC: Propionibacterium aches infection in neurosurgical patients. Med J Aust 145:408-410, 1986 8. Davidson HD, Steiner RE: Magnetic resonance imaging in infections of the central nervous system. AJNR 6: 499-504, 1985 9. Derakhshan I, Lotfi J, Kaukfman B: Ophthalmoplegia, ataxia and hyporeflexia (Fisher's syndrome) with a midbrain lesion demonstrated by CT scanning. Eur Neurol 18:361-366, 1979 10. Duffy PE, Sassin JF, Summers DS, et al: Rhombencephalitis due to Listeria monocytogenes. Neurology 14: 1067-1072, 1964 11. Everett ED, Eickhoff TC, Simon RH: Cerebrospinal fluid shunt infections with anaerobic diphtheroids. (Propionibacterium species.) J Neurosurg 44:580-584, 1976 12. Forward KR, Fewer D, Stiver HG: Cerebrospinal fluid shunt infections. A review of 35 infections in 32 patients. J. Neurosurg. / Volume 7 2 / A p r i l , 1990
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J Neurosurg 59:389-394, 1983 13. Frank JA, Friedman HS, Davidson DM, et at: Propionibacterium shunt nephritis in two adolescents with medulloblastoma. Cancer 52:330-333, 1983 14. French RS, Ziter FA, Spruance SL, et at: Chronic meningitis caused by Propionibacterium aches. A potentially important clinical entity. Neurology 24:624-628, 1974 15. Furman JM, Brownstone PK, Baloh RW: Atypical brainstem encephalitis: magnetic resonance imaging and oculographic features. Neurology 35:438-440, 1985 16. Gaida JB: Pontile abscess. Arch Otolaryngol 30:93-95, 1939 17. Harvey FH, Carlow T J: Brainstem abscess and syndrome of acute tegmental encephalitis. Ann Neurol 7:371-376, 1980 18. Hosoda K, Tamaki N, Masumura M, et at: Magnetic resonance images of brain-stem encephalitis. Case report. J Neurosurg 66:283-285, 1987 19. Hulme A: Suppurative lesions of the brainstem. J Neurol Neurosurg Psychiatry 24:291-293, 1961 20. Jachuck SJ, Gardner-Thorpe C, Clark F, et al: A brainstem syndrome associated with Mycoplasma pneumoniae infection. Postgrad Med J 51:475-477, 1975 21. Kaplan K, Weinstein L: Diphtheroid infections in man. Ann Intern Med 70:919-929, 1979 22. Kashiwagi S, Abiko S, Aoki H: Brainstem abscess. Surg Neurol 28:63-66, 1987 23. Kennard C, Howard AJ, Scholtz C, et al: Infection of the brainstem by Listeria monocytogenes. J Neurol Neurosurg Psychiatry 42:931-933, 1979 24. Noble WC: Microbiology of Human Skin. London: Lloyd-Luke Medical, 1981, pp 115-151,366-375 25. Parker RL, Collins GH: Intramedullary abscess of the brain stem and spinal cord. South Med J 63:493-497, 1970 26. Raimondi A J, Clark SJ, McLone DG: Pathogenesis of aqueductal occlusion in congenital murine hydrocephalus. J Neurosurg 45:66-77, 1976 27. Rekate HL, Ruch T, Nulsen FE: Diphtheroid infections of cerebrospinal fluid shunts. The changing pattern of shunt infection in Cleveland. J Neurosurg 52:553-556, 1980 28. Ropper AH: Three patients with Fisher's syndrome and normal MRI. Neurology 38:1630-1631, 1988 29. Rosenblum ML, Hoff JT, Norman D, et al: Nonoperative treatment of brain abscesses in selected high-risk patients. J Neurosurg 52:217-225, 1980
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30. Russell DS: Observations on the Pathology of Hydrocephalus. Medical Research Council Special Report Series 265. London: H M Stationery Office, 1949 31. Sandyk R, Brennan MJW: BickerstalTs brainstem encephalitis in Johannesburg. S Afr Med J 64:179-180, 1983 32. Schlesinger J J, Ross AL: Propionibacterium aches meningitis in a previously normal adult. Arch Intern Med 137:921-923, 1977 33. Shellshear 1, Emery JL: Gliosis and aqueductule formation in the aqueduct of Sylvius. Dev Med Child Neurol 18 (Suppl 37):22-28, 1976 34. Skinner PR, Taylor A J, Coakham H: Propionibacteria as a cause of shunt and postneurosurgicat infections. J Clin Pathol 31:1085-1090, 1978 35. Strand CL, Dubois RE: Propionibacterium acnes central nervous system shunt infection. Am J Clin Pathol 75: 743-746, 1981 36. Tachi N, Tsuzuki Y, Minami R: A case of brainstem encephalitis with CT scan abnormality mimicking Fisher syndrome. Brain Dev 8:538-541, 1986 37. Trautmann M, Wagner J, Chahin M, et at: Listeria meningitis: report of 10 recent cases and review of current therapeutic recommendations. J Infect 10:107-114, 1985 38. UenoT, TakahataN: Chronic brainstem encephalitis with mental symptoms and ataxia. J Neurol Neurosurg Psychiatry 41:516-524, 1978 39. Ueunten D, Tobias J, Sochat M, et at: An unusual cause of bacterial meningitis in the elderly: Propionibacterium acnes. Arch Neurol 40:388-389, 1983 40. VanEk B, Bakker FP, van Dulken H, et al: Infections after craniotomy: a retrospective study. J Infect 12: 105-109, 1986 41. VanGilder JC, Allen WE III, Lesser RA: Pontine abscess: survival following surgical drainage. Case report. J Neurosurg 40:386-390, 1974 42. Waxman SG, Sabin TD, Embree SJ: Subacute brainstem encephalitis. J Neurol Neurosurg Psychiatry 37: 811-816, 1974
Manuscript received July 10, 1989. Address reprint requests to: Paul J. Camarata, M.D., Department of Neurosurgery, University of Minnesota, Box 96 UMHC, B590 Mayo Memorial Building, 420 Delaware Street S.E., Minneapolis, Minnesota 55455.
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