Acute Severe Spinal Cord Dysfunction in Bacterial Meningitis in Adults MRI Findings Suggest Extensive Myelitis

OBSERVATION Acute Severe Spinal Cord Dysfunction in Bacterial Meningitis in Adults MRI Findings Suggest Extensive Myelitis

Stefan Kastenbauer, MD; Frank Winkler, MD; Gunther Fesl, MD; Xaver Schiel, MD; Helmut Ostermann, MD, PhD; Tarek A. Yousry, MD, PhD; Hans Walter Pfister, MD, PhD

Background: Bacterial meningitis is rarely compli- the cervical to the lumbar cord. Leptomeningeal and dis- cated by acute spinal cord involvement (eg, myelitis, is- crete nodular intramedullary enhancement on T1- chemic infarction, spinal abscess, or epidural hemor- weighted images was detected only in 1 patient. Fol- rhage). In spinal cord dysfunction, magnetic resonance low-up examinations revealed that hyperintensities imaging (MRI) is the imaging modality of choice. Still, resolved completely in 1 patient, while a central cavita- MRI findings of myelitis due to bacterial meningitis in tion developed in the cervical spinal cord of another, and adults have not been reported. the MRI findings were progressive during the first 4 weeks in the third patient. In all cases, severe paresis and bowel Methods: Spinal MRIs were obtained during the acute and bladder incontinence persisted. stage of meningitis and on follow-up in 3 adults with bacterial meningitis that was complicated by paraparesis or Conclusion: We demonstrate for the first time the MRI tetraparesis and bowel and bladder incontinence. The findings of adults with acute spinal cord involvement dur- causative pathogens were Streptococcus pneumoniae and ing bacterial meningitis. Magnetic resonance imaging Neisseria meningitidis; in 1 patient, the pathogen was not showed central intramedullary hyperintensities on T2- identified. weighted images that extended from the cervical to the lumbar cord, indicating myelitis. Clinical follow-up ex- Results: In all cases, spinal MRI ruled out a compres- aminations suggest that myelitis during bacterial men- sion of the cord by an extramedullary mass but demon- ingitis has an unfavorable prognosis. strated hyperintensities on T2-weighted images that predominantly involved the gray matter and extended from Arch Neurol. 2001;58:806-810

ACTERIAL MENINGITIS is fre- We describe 3 patients who devel- quently accompanied by oped severe spinal cord dysfunction dur- intracranial complications, ing the acute stage of bacterial meningi- such as cerebrovascular tis and their MRI findings during this involvement, brain edema, condition. hydrocephalus,B or hearing impairment, as well as systemic complications, such REPORT OF CASES as septic shock, adult respiratory distress syndrome, or disseminated intravascular CASE 1 coagulation.1-3 Spinal cord involvement is a rare complication of bacterial menin- A 36-year-old woman was admitted to a gitis.4 Besides cord compression by a local hospital with a 4-day history of fe- spinal abscess or epidural hemorrhage ver, back pain, and weakness of both legs. following lumbar puncture, the cord can be affected by ischemia due to vascu- For editorial comment litis, shock, herniation, or arachnoiditis, From the Departments of and by myelitis.4 Spinal magnetic reso- see page 717 Neurology (Drs Kastenbauer, nance imaging (MRI) during the acute Winkler, and Pfister), stage of spinal cord dysfunction has been Three years previously, she had under- Neuroradiology (Drs Fesl and reported in only 2 children: no abnor- gone splenectomy for idiopathic throm- Yousry), and Internal Medicine 4 (Drs Schiel and Ostermann), malities were detected in one child, and bocytopenic purpura, and 3 months prior Klinikum Großhadern, enhancement of the cauda equina and to admission, she had received her last Ludwig-Maximilians lumbosacral nerve roots was seen in the pneumococcal vaccination. On admis- University, Munich, Germany. other.5 sion, the patient was febrile, agitated, and

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 confused. Neurologic examination revealed neck stiff- travenous treatment with ceftriaxone was started. His CSF ness, an incomplete bilateral sixth nerve palsy, and a tet- contained 300 cells/µL (71% granulocytes), the protein raparesis (muscle power grade, 4/5 in the arms and 2/5 level was 1.66 g/L, and the CSF glucose level was less than in the legs). Muscle tone and tendon reflexes were de- 40% of the serum glucose level. There were no findings creased in the legs compared with the arms. The plantar on Gram stain and cultures from CSF and blood, but DNA response of the left foot was extensor. Blood cultures were from Neisseria meningitidis was detected in the CSF and positive for Streptococcus pneumoniae. Intravenous ben- blood by polymerase chain reaction. When sedation and zylpenicillin and ceftriaxone were administered, and the ventilator support were discontinued 5 days after admis- patient was transferred to our hospital. The cerebrospi- sion, flaccid paraplegia and a sensory level at T8 were nal fluid (CSF) contained 792 cells/µL (94% granulo- noted. The patient was given intravenous prednisolone cytes), the protein level was 6.3 g/L, and the CSF glu- (150 mg/d for 3 days, then 75 mg/d) for suspected my- cose level was less than 10% of the serum glucose level. elitis. Seventeen days after onset, the patient was trans- Gram-positive diplococci were present in the CSF, and ferred to our department. Despite repeated corticoste- the latex agglutination test result was positive for pneu- roid treatment, the spinal cord dysfunction was mococcal antigen; however, CSF cultures remained ster- progressive until 4 weeks after onset. Seven weeks after ile. Because myelitis was suspected, the patient was given onset, the patient still had a flaccid tetraparesis (muscle intravenous dexamethasone (24 mg/d) for 4 days. The power grade, 4/5 in the arms and 0/5 in the legs) and a clinical course was further complicated by ischemic in- sensory level at T6. Furthermore, bowel and bladder infarction in the right frontal lobe due to cerebral vascu- continence were present. litis. Three months after the onset of disease, the patient had a spastic tetraparesis (muscle power grade, 4/5 in the METHODS arms and 2/5 in the legs). Sensibility was intact, but bladder and bowel control were still absent. In all patients, MRI was performed on a 1.5-T MRI scan- ner (Magnetom Vision; Siemens, Munich, Germany). CASE 2 Detailed information on the sequences is given in the figure legends. A 33-year-old man who had been hospitalized because of bronchitis and mild graft-vs-host disease of the liver RESULTS following allogeneic bone marrow transplantation for chronic myeloid leukemia 6 months previously devel- For all 3 patients, T2-weighted images showed intramed- oped fever and headache despite oral antibiotic therapy ullary hyperintensities during the acute stage of spinal (amoxicillin, ciprofloxacin, and fluconazole). Within 24 cord dysfunction (day 5 of meningitis/day 5 of spinal cord hours of admission, weakness of both legs and bowel and dysfunction in patient 1; day 2 of meningitis/day 2 of spi- bladder incontinence appeared. Examination revealed dis- nal cord dysfunction in patient 2; day 6 of meningitis/ crete neck stiffness, spastic paraplegia, and a sensory level after day 1 of spinal cord dysfunction in patient 3), which at C1. The CSF contained 2976 cells/µL (94% granulo- appeared to be most pronounced in the gray matter. The cytes, no malignant cells), the protein level was 1.07 g/L, signal abnormalities extended from the cervical to the lum- and the CSF glucose level was less than 40% of the se- bar cord in patients 1 and 2 and from the cervical to the rum glucose level. There were no findings on Gram stain thoracic cord in patient 3 (Figure 1 and Figure 2). of CSF, and cultures of blood and CSF were sterile. Trans- While swelling of the spinal cord was clearly evident in cranial Doppler sonography and cranial MRI were nor- patient 3, it was not observed in the other patients. In- mal. Nosocomial bacterial meningitis was suspected, and tense leptomeningeal and discrete nodular intramedul- the patient was treated with intravenous vancomycin, me- lary gadolinium enhancement was observed in patient 1 ropenem, metronidazole, and a 4-day regimen of oral but not in patients 2 and 3 (Figure 1A). On native T1- dexamethasone, 24 mg/d. Six weeks after onset of men- weighted images, the central spinal cord lesion ap- ingitis, follow-up examination showed a motor level at peared hypointense in patient 1 and isointense in pa- C8, with a power grade of 4/5 in the small muscles of tients 2 and 3. In none of the patients did we detect an the hand and 2/5 in the legs. No clear sensory level could intramedullary abscess or compression of the cord by a be determined, but sensibility and vibratory sense were mass, such as an epidural hemorrhage, extramedullary decreased in both legs. Bowel and bladder incontinence abscess, or subdural empyema. were still present. On follow-up, the intramedullary signal abnormalities had completely resolved in patient 2. In patient 1, the CASE 3 extensive hyperintensities had almost completely resolved by day 17 after onset of meningitis, but on day 24, A previously healthy 17-year-old boy was admitted to a a central hyperintense lesion was detected in the cervical local hospital with a 1-day history of fever, nausea, and spinal cord at the level of C6. This lesion was interpreted headache. Examination revealed no focal neurologic defi- to be a newly formed syrinx. In patient 3, the T2 signal ab- cit, but a discrete neck stiffness and a petechial rash on normalities that initially involved only the thoracic cord the trunk and extremities. Shortly after admission, he had extended to C4 by day 17 (Figure 2) and to C3 by day 29. a respiratory arrest, at which time no blood pressure could Furthermore, the high intensity of the T2 signal was sub- be detected. The patient required mechanical ventilator stantially unchanged in the thoracic and cervical cord support, sedation, and treatment with vasopressors. In- compared with day 17 after onset of meningitis.

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Figure 1. Patient 1 on day 5 of meningitis due to Streptococcus pneumoniae. A, Sagittal postcontrast T1-weighted image (repetition time [TR], 587 milliseconds; echo time [TE], 12 milliseconds) shows intense leptomeningeal enhancement and discrete intramedullary enhancement. Sagittal (B) (TR=3894 ms, TE=112 ms) and axial (C) T2-weighted images at the level of T8 (TR, 5700 milliseconds; TE, 120 milliseconds) show central intramedullary hyperintensities in the cervical, thoracic, and lumbar cord that predominantly involve the gray matter.

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 COMMENT Acute spinal cord dysfunction is a rare complication of bacterial meningitis; since 1971, 29 cases have been reported.4-7 Of these 29 patients, 4 were adults and 25 children. Causative pathogens were N meningitidis (n=10), S pneumoniae (n=6), Escherichia coli (n=5), Haemophi- lus influenzae (n=4), Streptococcus agalactiae (n=2), Kleb- siella pneumoniae (n=1), and Corynebacterium jeikeium (n=1). The most frequent initial symptom was quadriplegia or paraplegia. Spinal cord symptoms became evident from the time of diagnosis of meningitis until 4 days after the initiation of therapy. Six patients died, and only 3 of the 23 survivors had a complete neurological recov- ery. The most common residual deficits were spasticity and weakness, walking difficulties, and bowel and bladder dysfunction. Possible causes of spinal cord dysfunction in acute bacterial meningitis are mass effect, ie, cord compression, vascular compromise, or myelitis. Compression of the spinal cord was ruled out in all of the above-mentioned cases examined by myelogram (10 patients) or MRI (5 patients). Magnetic resonance imaging of the spinal cord during the acute illness was performed in 2 children. While spinal MRI was reported to be normal in one child,4 it showed enhancement of the cauda equina and lumbosacral nerve roots in the other,5 which was interpreted to be lumbosacral polyradiculopathy. Three patients were examined only later. Five weeks after the acute illness, cys- tic dilatation of the upper thoracic cord was present in one case,7 which was believed to be due to vasculitis. Seven weeks after onset of meningitis, atrophy of the cervical spinal cord was detected in another patient,8 and 1 year after meningitis, spinal MRI was reported to be normal in one patient.9 We first performed spinal MRI in our patients during the first days of meningitis and spinal cord involvement. The dominant finding—in addition to the exclusion of cord compression—was the high T2 signal in the central spinal cord, which appeared to predominantly involve the gray matter. A low intramedullary signal on T1- weighted images and discrete nodular contrast enhance- Figure 2. Patient 3 on day 17 of meningitis due to Neisseria meningitidis. ment of the cord were present only in patient 1. In view Sagittal T2-weighted image (repetition time, 3894 milliseconds; echo time, of the MRI findings and the exclusion of spinal cord com- 112 milliseconds) shows swelling of the cervical cord and central pression, the differential diagnoses for our patients were intramedullary hyperintensities in thoracic and cervical cord extending up to C4. venous congestion, ischemic infarction, and myelitis, alone or in combination. ceded manifestation of spinal symptoms in 12 of the Cerebral septic venous thrombosis is a well- above-mentioned cases and in 1 of the patients pre- recognized complication of purulent meningitis,10 and sented herein (patient 3). However, the respiratory ar- compromised venous drainage of the spinal cord due to rest and hypotension in this patient were probably not septic venous thrombosis or adhesive arachnoiditis is also the only cause of spinal cord dysfunction because MRI conceivable in meningitis. High T2 signals in the cen- signal abnormalities were progressive for 4 weeks after tral spinal cord are a common finding in venous conges- the event. Adhesive arachnoiditis with constriction of the tion, eg, because of spinal dural arteriovenous fistulas.11 spinal cord and putative interference with the blood sup- However, there is no pathological report of spinal ve- ply has been reported to occur from 10 days to several nous thrombosis in bacterial meningitis in the absence years after acute bacterial meningitis.12,13 However, ad- of myelitis. Nevertheless, it may have contributed to the hesive arachnoiditis seems unlikely in our patients, since spinal cord damage in our patients. spinal cord symptoms developed during the first days of Ischemic infarction of the cord during bacterial men- meningitis. Furthermore, the resolution of the exten- ingitis can be caused by vasculitis, systemic hypoten- sive intramedullar signal abnormalities in patients 1 and sion due to shock, or arachnoiditis with secondary vas- 2 at follow-up makes ischemia unlikely. culitis.4 Severe hypotension or shock, which may have Myelitis during purulent meningitis has been rarely contributed to vascular compromise of the cord, pre- demonstrated on postmortem examination. In particu-

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 lar, edema, focal hemorrhages, perivascular inflamma- Corresponding author and reprints: Hans Walter Pfis- tion in the subarachnoid space, capillary thrombosis, di- ter, MD, Department of Neurology, Ludwig-Maximilians latation and thrombosis of the anterior spinal artery, and University, Marchioninistrasse 15, 81377 Munich, Ger- myelomalacia have been reported.6,12,14-16 In 3 patients, many (e-mail: [email protected]). myelomalacia primarily affected the gray matter and 6,14 spared the white matter. In our patients, the high T2 REFERENCES signal possibly reflected edema due to inflammation, while discrete nodular contrast enhancement was seen only in 1. Pfister HW, Feiden W, Einhaupl KM. Spectrum of complications during bacterial patient 1. Enhancement was not observed in the other 2 meningitis in adults: results of a prospective clinical study. Arch Neurol. 1993; patients, possibly because of early antibiotic and anti- 50:575-581. inflammatory (steroid) therapy. 2. Roos KL. Bacterial meningitis. Curr Treat Options Neurol. 1999;1:147-156. On follow-up, signal abnormalities resolved in pa- 3. Tunkel AR, Scheld WM. Acute bacterial meningitis [review]. Lancet. 1995;346: tient 2. In patient 1, a small syrinx had developed in the 1675-1680. 4. Moffett KS, Berkowitz FE. Quadriplegia complicating Escherichia coli meningitis cervical cord (a known late complication of purulent in a newborn infant: case report and review of 22 cases of spinal cord dysfunc- 17 meningitis ). In patient 3, neurologic deficits and MRI tion in patients with acute bacterial meningitis [review]. Clin Infect Dis. 1997; alterations were progressive for 4 weeks. All 3 patients 25:211-214. had persisting tetraparesis and bowel and bladder incon- 5. Kikuchi M, Nagao K, Muraosa Y, Ohnuma S, Hoshino H. Cauda equina syndrome complicating pneumococcal meningitis. Pediatr Neurol. 1999;20:152-154. tinence, although MRI signal alterations of the cord had 6. Bouygues D, Sanmarti F, Ponsot G, Auberge C, Arthuis M. Mye´lopathies aigues resolved in 2 of them. In at least these 2 cases, the neu- au cours des me´ningites purulentes. Arch Fr Pediatr. 1980;37:103-107. rologic deficits must be attributed to diffuse damage to 7. Puvabanditsin S, Wojdylo EW, Garrow E, Kalavantavanich K. Group B strepto- the spinal cord, which cannot be discerned on MRI. coccal meningitis: a case of transverse myelitis with spinal cord and posterior In conclusion, we have demonstrated for the first fossa cysts. Pediatr Radiol. 1997;27:317-318. 8. Coker SB, Muraskas JK, Thomas C. Myelopathy secondary to neonatal bacterial time the MRI findings of adults with spinal cord involve- meningitis [review]. Pediatr Neurol. 1994;10:259-261. ment during bacterial meningitis. The observed exten- 9. Kirkpatrick M, Brooker RJ, Helms PJ, Cole GF. Spinal cord dysfunction in neo- sive central intramedullary hyperintensities and the fol- natal meningococcal meningitis. Eur J Pediatr. 1994;153:367-368. low-up MRIs (signal abnormalities resolved completely 10. Pfister HW, Borasio GD, Dirnagl U, Bauer M, Einhaupl KM. Cerebrovascular complications of bacterial meningitis in adults. Neurology. 1992;42:1497- in one patient, left a small syrinx in the cervical cord of 1504. another patient, and even progressed in the third pa- 11. Gilbertson JR, Miller GM, Goldman MS, Marsh WR. Spinal dural arteriovenous tient) are consistent with myelitis. Findings of clinical fistulas: MR and myelographic findings. AJNR Am J Neuroradiol. 1995;16:2049- follow-up examinations suggest that myelitis during bac- 2057. terial meningitis has an unfavorable prognosis. 12. Turner JWA. Spinal-cord lesions in cerebrospinal fever. Lancet. 1948;1:398-402. 13. Haupt HM, Kurlinski JP, Barnett NK, Epstein M. Infarction of the spinal cord as a complication of pneumococcal meningitis: case report. J Neurosurg. 1981;55: Accepted for publication September 9, 2000. 121-123. We thank Claudio Padovan, MD; Werner Scheuerer, 14. Tal Y, Crichton JU, Dunn HG, Dolman CL. Spinal cord damage: a rare compli- MD; Chrostoph Siebold, MD; Manfred Wick, MD; Beatrice cation of purulent meningitis. Acta Paediatr Scand. 1980;69:471-474. Grabein, MD; Hans-Jochem Kolb, MD, PhD; Maximilian Rei- 15. Banks HS, McCartney JE. Meningococcal encephalitis. Lancet. 1942;1:219-223. 16. Norman MG. Respiratory arrest and cervical spinal cord infarction following lum- ser, MD, PhD; Matthias Frosch, MD, PhD; and Hanns bar puncture in meningitis. Can J Neurol Sci. 1982;9:443-447. Lohner, MD, for their clinical cooperation. We also thank 17. Caplan LR, Norohna AB, Amico LL. Syringomyelia and arachnoiditis. J Neurol J. Benson for copyediting the manuscript. Neurosurg Psychiatry. 1990;53:106-113.

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