Neuroradiology (2003) 45: 634–639 DOI 10.1007/s00234-003-1035-8 W. Jan R.A. Zimmerman L.T. Bilaniuk J.V. Hunter E.M. Simon J. Haselgrove Received: 31 March 2003 Accepted: 31 March 2003 Published online: 8 August 2003 Ó Springer-Verlag 2003 W. Jan Æ R.A. Zimmerman (&) L.T. Bilaniuk Æ J.V. Hunter E.M. Simon Æ J. Haselgrove Department of Radiology, Children’s Hospital of Philadelphia, 34th Street & Civic Center, Boulevard, Philadelphia, PA 19104, USA E-mail: zimmerman@email.chop.edu Tel.: +1-215-5902569 Fax: +1-215-5901345 PAEDIATRIC NEURORADIOLOGY Diffusion-weighted imaging in acute bacterial meningitis in infancy Abstract Bacterial meningitis is frequently fatal or leads to severe neurological impairment. Complications such as vasculitis, resulting in infarcts, should be anticipated and dealt with promptly. Our aim was to demonstrate the complications of meningitis by diffusion weighted imaging (DWI) in patients who deteriorated despite therapy. We studied 13 infants between the ages of 1 day and 32 months who presented with symptoms ranging from fever and vomiting to seizures, encephalopathy and coma due to bacterial meningitis, performing MRI, including DWI, 2–5 days after presentation. Multiple infarcts were found on DWI in 12 of the 13, most commonly in the frontal lobes (in Introduction Meningitis may have profound effects on the brain parenchyma. Although antibiotics have been used successfully in eradicating the infecting organism in many cases, major neurologic complications continue to occur. Cerebral infarcts in the survivors of childhood bacterial meningitis are potentially serious, and relatively common, occurring in about 30% of cases [1]. For decades physicians have relied upon autopsy to determine the pathogenesis of the complications of meningitis, as routine imaging has failed to demonstrating subtle pathology [2]. Diffusion-weighted imaging (DWI) is a simple way of examining the vascular and neurologic complications of bacterial meningitis. 10). Global involvement was seen in four children, three of whom died; the fourth had a very poor outcome. In one case abnormalities on DWI were due to subdural empyemas. We diagnosed vasculitis in three of five patients studied with MRA. We think DWI an important part of an MRI study in infants with meningitis. Small cortical or deep whitematter infarcts due to septic vasculitis can lead to tissue damage not easily recognized on routine imaging and DWI can be used to confirm that extra-axial collections represent empyemas. Keywords Infants Æ Bacterial meningitis Æ Diffusion-weighted imaging DWI is said to provide a means of identifying cytotoxic edema, through reduction in the diffusion of protons, caused by acute ischemia or infarction. The edema gives bright signal on DWI, and this is believed to reflect increased intracellular and decreased extracellular fluid resulting from sodium-pump failure. Vasogenic or interstitial edema, on the other hand, are thought to be associated with unchanged or decreased signal, with evidence of increased diffusion on maps of apparent diffusion coefficients (ADC). We report our 4-year experience with DWI in acute bacterial meningitis in children and discusses the implications of diagnosing cerebral infarcts. 635 Materials and methods We studied 13 children with meningitis whose clinical condition deteriorated acutely, despite appropriate therapy (Table 1). There were seven boys and six girls aged between 1 day and 32 months, most less than 5 months. Microbiological confirmation of the diagnosis was established in all but patients except case 13, where the diagnosis was based on the cerebrospinal fluid (CSF) profile. MRI was performed at 1.5 tesla during the acute illness, 1–5 days after the onset of symptoms. It included axial and coronal T2-weighted and sagittal and coronal T1-weighted images, coronal fluid-attenuated invesion-recovery and contrast-enhanced T1-weighted images in three orthogonal planes. MR angiography (MRA) was performed in five cases. Axial DWI was performed using a single-shot echoplanar spin-echo technique. Diffusion gradients were applied in x, y, and z directions with four b values ranging between 0 and 1000 s/mm2. The data were then used to derive ADC maps. The diagnosis of infarct was based on DWI evidence of single or multiple foci of restricted diffusion and low ADC. Results We saw one or more infarcts in 12 of the 13 infants (Table 2); in patient 4, all abnormalities on DWI were related to bilateral subdural empyemas. The frontal lobes were most commonly involved (10 of 12 patients), and the infarcts were predominantly bilateral (Fig. 1). In patient 3 the frontal lobe infarcts became infected. Global abnormalities on DWI with particular involvement of the posterior cranial fossa structures were seen Table 1 Microbiology and clinical features Patient, age, sex Pathogen Presentation Duration of admission Outcome 1. 1 day, M 2. 4 days, M 3. 5 days, F 4. 11 days, M 5. 2 weeks, F 6. 4 weeks, M 7. 5 weeks, F 8. 2 months, F 9. 4 months, F 10. 5 months, F 11. 5 months, M 12. 22 months, M 13. 32 months, F Escherichia coli Group B streptococcus Citrobacter koserii Group A streptococcus Group B streptococcus Pasteurella multocide Group B streptococcus Group B streptococcus Pseudomonas aeruginosa Streptococcus pneumoniae Streptococcus pneumoniae Group B streptococcus No growth Fever, tonic seizures Sleepy, twitching of arms Irritable, inconsolable Fever, seizures Lethargy, seizures Fever, vomiting, left leg shaking Fever, seizures Fever, vomiting, lethargy Fever, lethargy, respiratory distress Fever, vomiting, diarrhea, irritability Lethargy, otitis media, tonic/clonic seizures Altered consciousness, right hemiparesis Cough, fever, petechial rash, lethargy 4 days 14 days 18 days 12 days 13 days 30 days 20 days 15 days 3 days 11 days 7 days 6 days 9 days Died Good recovery Poor Good recovery Poor Good recovery Poor Very poor Died Good recovery Poor Died Good recovery Table 2 Abnormalities on MRI and diffusion-weighted imaging (DWI) Patient Day Empyema of MRI Brain lesions Vascular Territories Vasculitis MRA Perfora- Large Watershed tors vessel 1 2 3 3 5 5 No No No 4 5 9 4 Multiple No 6 7 2 2 No No 8 9 10 11 4 2 4 1 No No Left No 12 2 3 5 5 Yes Multiple infarcts Unchanged Multiple infarcts Unchanged Diffuse infarcts No Single infarct 13 Diffuse infarcts + Multiple infarcts + Multiple hemorrhagic infarcts None Multiple infarcts + Multiple infarcts + Multiple hemorrhagic infarcts Multiple infarcts + Diffuse infarcts + Multiple infarcts + Multiple infarcts + + + + + + + + + + Global Basal ganglia Bifrontal (abscesses) + + No None Left thalamus, parietal lobe, splenium Bifrontal, bitemporal, thalamus Bifrontal, left parietal + + ++ ++ No + + + + ++ Progression ++ Global Global Diffuse supratentorial and vermis Bitemporal, hypothalamus, deep white matter Left frontal, biparietal, splenium Left carotid territory, basal ganglia Global Left frontal 636 Fig 1A, B Case 6: meningitis with infarcts in territory of perforating arteries. A Axial T2-weighted image does not show an infarct. A subdural hygroma is seen on the right. B Diffusion-weighted imaging (DWI) shows multiple small infarcts as areas of restricted diffusion (arrows) in the deep white matter in four patients, three of whom died, while the fourth had a very poor outcome (Fig 2). Vasculitis was confirmed by MRA in three of the five patients in whom it was performed and in patient 12 this proved to be rapidly progressive despite therapy (Fig. 3). The five patients who had a favorable outcome developed only a few minute scattered lesions. Group B streptococcus was isolated in five patients and Streptococcus pneumoniae in two. Escherchia coli, citrobacter, pseudomonas, group A streptococcus and Pasteurella multocide were isolated in one patient each. Discussion Bacterial meningitis still has high mortality and morbidity rate and central nervous system complications occur in as many as 40% of cases [3]. Despite advances in antibiotic treatment, the morbidity has not lessened [4]. Sequelae such as hearing loss, paresis, epilepsy, hydrocephalus, and psychomotor retardation are still reported and more subtle deficits such as behavioral and academic difficulties are more prevalent among children who had meningitis in infancy [5]. Cerebral infarcts are a well-known sequel of meningitis, occurring in as many as 10–20% of patients [6]. The frequency is higher in the children, approximately 30%, which may contribute to the poor prognosis of neonatal meningitis. Focal thalamic, pontine or upper spinal cord infarcts have been reported as an early manifestation of meningitis [7, 8]. The underlying mechanisms are vasculitis, thrombosis, arachnoiditis and compression of the arterial supply at the foramen magnum by herniation of the cerebellar tonsils [9]. Concomitant hypotension can contribute to the damage [10]. Vasculitis associated with infections of the central nervous system is part of the subarachnoid inflammation. Its severity and the potential for permanent complications are thought to increase in relation to the time between the onset of infection and successful treatment and complete resolution of inflammation [11]. However, infarcts are not a late complication, as they most often appear 1–6 days after infection. Autopsy findings in cases of bacterial meningitis with onset under 3 months of age have recorded multiple large randomly situated infarcts, which involve the entire thickness of the cortex and extend deep into the white matter, while smaller ischemic infarcts were seen in the midbrain and thalamus [1]. There is elevation of the intima by accumulated polymorphonuclear leukocytes, leading to reduction in diameter of the lumen. The vessel wall may become necrotic and undergo thrombosis. The subacute and chronic stages are proliferative, leading to partial or total destruction of the internal elastic lamina with reduction in the lumen of larger vessels. This can result in weakening of the vessel wall and the formation of mycotic aneurysms. The veins can also be inflammed, leading to generalized phlebitis and thrombosis with or without parenchymal hemorrhage [11]. Sinus thrombosis is uncommon [1]. Common organisms causing vasculitis as a complication of meningitis are group B streptococcus, Hemophilus influenzae, Pseudomonas aeruginosa, Salmonella enteridis, Streptococcus pneumoniae, and Streptococcus anginosus [7, 11, 12, 13]. Focal cerebral infarcts with necrosis might 637 Fig 2A, B Case 8: meningitis with vasculitis and extensive hemisphere infarcts. A DWI showing diffuse reduction in apparent diffusion coefficients (ADC) in the temporal and occipital lobes, with involvement of the vermis. B Probable narrowing of the basilar artery (arrow) on MR angiography (MRA) mimic an abscess particularly in citrobacter meningitis where they are commonly hemorrhagic. Surgical drainage of such lesions could lead to further damage to the relatively preserved overlying cortex [14]. However, the possibility of abscess formation due to secondary infection of the infarcts should be considered, as in our patient 3. Although CT can demonstrate major complications of meningitis such as brain edema, infarcts, hydrocephalus, subdural pathology and brain abscess [15], it is insensitive to subtle changes [2]. MRI can define the site and extent of infarcts [16] and is more sensitive than CT [17] to inflammatory vasculitis. However, small cortical and deep white-matter infarcts that lead to subtle tissue damage are not always recognized on routine MRI. In the infant’s brain, where the white matter is not myelinated, identification of small infarcts can be very difficult. Thus, DWI can play an important part in the investigation of young children with meningitis. DWI shows diffusion of water molecules and is used in acute stroke, where shortly after an episode of ischemia, diffusion is highly restricted due to shift of fluid into the intracellular compartment, with cytotoxic edema. 638 Fig 3A–D Case 12: meningitis with progressive vasculitis and both perforatingr and major vessel territory infarcts. A sudden deterioration in DWI findings is associated with evidence of rapidly progressive vasculitis. A ADC map showing small bilateral infarcts (arrows) in the hypothalamus. There is hydrocephalus. B MRA showing narrowing (arrows) of the right anterior and both middle cerebral arteries (MCAs). C ADC map 1 day later showing a left MCA territory infarct. D Contemporary MRA progression of the vasculitis with occlusion of the left MCA, narrowing of the distal right internal carotid artery (arrow), and further narrowing of right anterior and middle cerebral arteries The ADC of brain tissue is significantly reduced in acute cytotoxic edema but over several days, the rapid initial fall followed by ‘‘pseudonormal’’ values at approximately 1 week and subsequent elevation in the chronic phase [18]. Regions of vasogenic edema have increased ADC because diffusion of water in the extracellular component is less than in free water but significantly higher than in the intracellular compartment [19]. ‘‘T2 shine-through’’ must be considered when there is high signal on DWI; lesions which give high signal on T2-weighted images can also appear bright on DWI. However, when ADC maps shows restricted diffusion, T2 shine-through is not likely to be the cause of high signal. Small cortical and deep white-matter infarcts due to septic vasculitis were seen in 12 out of 13 patients. Most infarcts were in the frontal lobes, the largest of the cerebral lobes, which may also relate to the large overlying subarachnoid space in which the arachnoid inflammation produces the vasculitis. The size, site and multiplicity of the infarcts correlate with outcome. Involvement of the infratentorial structures carries a poor outcome, while patients with a favorable outcome developed only a few minute scattered lesions. An added advantage to DWI is its ability to confirm extra-axial empyemas. They give high signal on DWI have markedly diminished ADC (Fig. 4), in contrast to reactive effusions, that give low signal and show only mild reduction of ADC. The restricted diffusion of empyemas could be a reflection of their high protein content, hindering movement of water. 639 Fig 4A, B Case 4: meningitis with subdural hygromas and empyemas, but no infarct. 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