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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 3  |  Page : 228-233

Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique


1 Department of Radiology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
2 Department of Medicine, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
3 Department of Infectious Diseases, Christian Medical College and Hospital, Vellore, Tamil Nadu, India
4 Department of Medicine, St. Vincent Hospital, Worcester, MA, USA
5 Department of Radiology, Jerudong Park Medical Center, Bandar Seri Begawan, Brunei

Date of Submission24-May-2021
Date of Acceptance23-Jul-2021
Date of Web Publication03-Sep-2021

Correspondence Address:
Harshad Arvind Vanjare
Department of Radiology, Christian Medical College and Hospital, Ida Scudder Road, Vellore - 632 004, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_117_21

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  Abstract 


Background: Tuberculous meningitis (TBM) is a global health problem with important complications such as acute infarcts secondary to vasculitis contributing to adverse outcomes. The objective of this study is to assess intracranial vasculitis in patients with TBM, either during their initial diagnosis or during follow-up while on standard antituberculous therapy. Methods: Ten patients with TBM underwent magnetic resonance (MR) based vessel wall imaging (VWI) to identify intracranial vasculitis (five patients during their initial presentation and the other five patients during their follow-up visit). Results: Vasculitis was seen in 60% of the patients wherein 70% of their intracranial vessels were affected. Acute and chronic infarcts were seen in four and two patients respectively, one of whom had both acute and chronic infarcts. Leptomeningeal enhancement and basal cisternal tuberculomas were frequently seen in patients with vasculitis. Vasculitis was also seen many days after the commencement of the antituberculous therapy thus explaining late-onset infarcts in this disease. Conclusion: Intracranial vasculitis is common in the patient with TBM. MR-based VWI technique has the potential for infarct risk assessment and to help guide the treatment for its possible prevention.

Keywords: Infarcts, tuberculosis, tuberculous meningitis, vasculitis, vessel wall imaging


How to cite this article:
Vanjare HA, Gunasekaran K, Manesh A, Mishra AK, Mannam P, Iyadurai R, Jasper A, Mani S. Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique. Int J Mycobacteriol 2021;10:228-33

How to cite this URL:
Vanjare HA, Gunasekaran K, Manesh A, Mishra AK, Mannam P, Iyadurai R, Jasper A, Mani S. Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique. Int J Mycobacteriol [serial online] 2021 [cited 2021 Oct 28];10:228-33. Available from: https://www.ijmyco.org/text.asp?2021/10/3/228/325491




  Introduction Top


Tuberculosis (TB) is caused by the bacillus Mycobacterium TB. This bacillus causes asymptomatic infection in a quarter of the world population, thus putting them at risk of developing the tuberculous disease in the presence of poor nutrition, socio-economic deprivation, and immunosuppression.[1] In 2019, 1.2 million people died due to TB worldwide.[1] Globally, an estimated 10 million people fell ill with TB in 2019.[1] One percent of the individuals with systemic TB develop the central nervous system TB which is often in the form of parenchymal tuberculomas.[2] The subpial tuberculomas can rupture into the subarachnoid space leading to tuberculous meningitis (TBM) and is considered to be the main mechanism for its development.[3] Cerebral infarction is an important complication of TBM affecting up to two-thirds of the patients[4] and is associated with poor outcomes.[5] TB predominantly causes exudates along the basal surface of the brain and adjacent cisternal spaces; however, the majority of the infarcts are in perforator arteries of both the anterior and posterior circulation.[2],[4],[5] Earlier, pathology studies have shown intracranial vasculitis with mononuclear cell infiltration involving vessels in close vicinity to the tuberculous lesions, affecting the adventitia more than the media.[6] Autopsy studies have also shown extensive vasculitis in TBM involving both the proximal vessels of the circle of Willis and distal perforator branches.[7] There is inadequate imaging literature assessing vasculitis in patients with TBM. Vessel wall imaging (VWI) is a relatively new magnetic resonance imaging (MRI)-based technique to identify intracranial vasculitis by assessing concentric vessel wall enhancement.[8] Thus, VWI can be used to assess the extent of vasculitis in TBM.


  Methods Top


This single-center observational (prospective cohort) study from a medical college hospital in South India was performed after obtaining clearance from the institutional ethics board (IRB Min No: 10372). Newly diagnosed patients with TBM were recruited after informed consent. Clinically stable patients (with stable vital signs and who could cooperate for the study) underwent VWI during their first admission. The clinically unstable patient (any patient who was restless requiring sedation, intubated, or requiring supplemental oxygen by mask to maintain normal blood oxygen saturation, the patient with hypotension requiring inotropic support to maintain blood pressure) underwent VWI during their follow-up visit after they had been initiated on antituberculous therapy. All the VWI studies were performed concurrently with the routine MRI brain studies.

Imaging protocol for vessel wall imaging

All the studies were performed on a Philips Achieva 3.0 Tesla scanner. Pre and postcontrast images in three standard orthogonal planes (axial, coronal, and sagittal) were acquired using a 2D double inversion recovery black-blood technique (relaxation time 2100 ms, inversion time [860 ms, echo time 12 ms, voxel size 0.44/0.44/2.00 mm, slice gap 2 mm, maximum slices 42, and a field of view 210 mm × mm 159 × 88 mm) with a total scan duration of 14 min 44 s. Inj. Clariscan (gadoterate meglumine) at the dose of 0.1 mmol/kg body weight was administered as a manual intravenous bolus injection and the postcontrast study was acquired after 30 s. The sequences were planned such that the entire circle of Willis was included in the field of view. Sequences included in the routine MRI imaging of the brain were T2-weighted (T2W) axial and coronal, T2-weighted-Fluid-Attenuated Inversion Recovery (T2 FLAIR) axial, T1-weighted (T1W) coronal and sagittal, diffusion, and susceptibility-weighted sequences.

Imaging analysis

Images were reviewed by two radiologists with 5 and 3 years of experience in neuroradiology and findings were documented by consensus. Any disagreement was resolved by consulting with a senior radiologist with 10 years of experience in neuroradiology. Eleven vessels (intracranial portion of bilateral vertebral arteries, basilar artery [BA], P1 and proximal P2 segments of bilateral posterior cerebral arteries, cavernous and supra-cavernous segments of bilateral internal cerebral arteries, M1 and proximal M2 segments of bilateral middle cerebral arteries [MCA,] and A1 and proximal A2 segments of bilateral anterior cerebral arteries [ACA]) were assessed for concentric wall enhancement as a marker for vasculitis.


  Results Top


Ten patients (five male and female each) with features of TBM and an average age of 33.5 (median 32, range 17–58) years were enrolled in the study from 2017 to 2019 [Table 1] and [Table 2]. TBM was classified based on the modified Thwaites criteria[9] into definite, probable, and possible with two, three, and five cases in each group, respectively. The presenting complaints, in descending order of frequency, were headache, fever, vomiting, altered sensorium, and seizures.
Table 1: First presentation

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Table 2: Follow up

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Five clinically stable patients underwent routine MRI brain studies with concurrent VWI during their first hospital admission at an average interval of 9 (median 8, range 1–23) days after initiation of the standard antituberculous therapy with steroids. At follow-up, four of these patients showed remarkable clinical improvement, and therefore repeat routine imaging of the brain was not performed. Follow-up imaging was done in one patient in this group who continued to be symptomatic for TBM.

The other five patients who were clinically unstable at the initial presentation did not undergo VWI studies during the first visit which was deferred to their second follow-up visit. These patients underwent VWI studies at an average interval of 167.6 (median 73 and range 60–473) days after the initiation of standard antituberculous therapy and steroids (steroids were given for 2 months during the initial intensive phase of antituberculous therapy).

Vasculitis was seen in six (60%) patients affecting 46 of 110 (42%) of intracranial vessels examined [Figure 1], of these two (40%) patients had vasculitis during their first visit, while four (80%) patients had vasculitis during their second visit. In patients with vasculitis, the basilar artery (BA) and left vertebral artery (VA) were most affected and was seen in all six (100%) patients. ACA was the least commonly affected vessel (in these patients), affecting two of the six (33%) patients. During the first visit, 13 of the 55 (24%) vessels in five patients showed vasculitis, against 33 of 55 (60%) in the other five patients who were imaged during their second visit.
Figure 1: Precontrast (a-c) and postcontrast (d-f) double inversion recovery black-blood sequence (vessel wall imaging) in different patients demonstrating concentric wall enhancement in the bilateral anterior cerebral arteries (d), basilar artery (e) and supracavernous segment of the right internal cerebral arteries (f) suggestive of vasculitis

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Acute infarcts were seen in four (40%) patients during their first routine imaging as areas of diffusion restriction. Two of these patients underwent VWI during the same sitting. Both patients had acute lacunar infarcts involving a single lentiform nucleus with vasculitis of bilateral MCA in one patient and ipsilateral MCA in the other patient on VWI. The other two patients had acute infarcts involving the midbrain and lacunar infarcts involving bilateral deep cerebral white matter in the frontal and parietal lobes in one patient, and left side of the pons and superior aspect of the left cerebellar hemisphere in the other patient [Figure 2]. The follow-up VWI study did not demonstrate vasculitis in the first patient; whereas vasculitis of the BA was seen in the second patient at 2.5 months of follow-up, respectively.
Figure 2: 35-year-old male with tuberculous meningitis at first presentation. Axial T2W (brain) image (a) shows hyperintensity involving the left side of pons and adjacent left superior cerebellar hemisphere. Corresponding areas shows diffusion restriction (diffusion and ADC map) images (b and c) suggestive of an acute infarct. Postcontrast T1W axial section shows enhancement along the left ambient cistern and along the tentorium (d). Follow up vessel wall imaging study after 2.5 months shows worsening of the disease with exudates and tuberculomas filling up the basal cisternal cerebrospinal fluid spaces. Enhancement is seen involving the wall of left posterior cerebral arteries suggestive of vasculitis (black arrow images (e and f). The BA is embedded within the inflammatory tissue (arrowhead). Third imaging, image (g) after 7 months of the initial presentation showed near-complete resolution of basal exudates and tuberculomas with residual gliotic changes involving the brainstem and cerebellum

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Six of the 10 patients returned for follow-up imaging (one from the stable group and five those who were initially unstable). Newer infarcts were seen in three patients, all with vasculitis. One patient had an acute infarct involving the left lentiform nucleus. This patient underwent VWI during the first visit (1 month prior) which had shown vasculitis involving bilateral MCA and an acute infarct involving the contralateral lentiform nucleus. The other two patients had VWI studies during their second follow-up visits. One patient has chronic infarcts in the left lentiform and caudate nuclei (not seen in the initial study done 16 months prior) with vessel wall enhancement suggestive of active vasculitis in the left MCA. The second patient had a new chronic infarct in the midbrain with vasculitis involving the BA, where at initial imaging without VWI, acute infarcts were seen only in the left pons and left superior cerebellum.

Brain stem abnormality was seen in six (60%) patients during initial imaging. Three patients had edema secondary to tuberculomas along the surface of the brainstem, two patients had tuberculomas involving the brainstem with associated edema, while one patient had brainstem tuberculoma in addition to an infarct. One of these patients underwent VWI during the initial presentation; while the other five patients were clinically unstable and therefore underwent VWI during follow-up. On follow-up, one patient has worsening of brainstem edema with an increase in the number and size of basal cisternal tuberculomas, while the other four patients showed improvement.

Leptomeningeal enhancement was seen predominantly along the basal cisternal spaces in all six patients with vasculitis, five of whom also had tuberculomas in these spaces. Parenchymal granulomas were ring-enhancing lesions in four of the six (67%) patients with vasculitis against two of the four (50%) patients without vasculitis. Hydrocephalus was seen in six of the 10 (60%) patients during the initial imaging, of which five patients also had vasculitis. All these patients underwent follow-up imaging with either stable caliber of the ventricular system without transependymal cerebrospinal fluid seepage or interval reduction in hydrocephalus.


  Discussion Top


TBM is known to cause intracranial vasculitis which can be associated with infarcts.[10] Autopsy studies have shown extensive vasculitis in patients with TBM and can be divided into necrotizing, infiltrative, and proliferative lesions.[7],[11] While necrotizing and infiltrative lesions develop early in the disease; proliferative lesions have a late-onset causing luminal narrowing.[7] Extensive involvement of both the proximal larger and distal smaller vessels have been previously demonstrated in pathology studies with the presence of macroscopic infarcts in the anterior vascular territories, predominantly affecting the basal ganglia, and microscopic infarcts in the posterior vascular territories predominantly affecting the brainstem.[7] Few digital subtraction angiography and magnetic resonance (MR) angiography studies in patients with TBM have also shown vascular abnormalities involving the proximal major intracranial vessels in 45%–51% of cases; however, these studies are limited by their assessment of luminal narrowing or irregularity which fails to identify vasculitis in the absence of these findings.[12],[13] There is a single case report where serial VWI studies in a child with TBM showed extensive vasculitis involving the vessels of the circle of Willis with gradual resolution of vessel wall enhancement over 237 days of follow-up.[14]

In our study, patients were enrolled either during their first or second follow-up visit depending on their clinical status. This has allowed us to assess vasculitis in a larger temporal space by assessing clinically stable patients who were more likely to have milder disease early on as compared to the clinically unstable patients who were more likely to develop a severe form of the disease, later on. The clinically unstable patients were more likely to have vasculitis (80%) as against those who were stable during the initial visit (40%). Late-onset infarcts are known to develop in patients with TBM[5] with an acute infarct involving the left lentiform nucleus seen in one of our patients at follow-up. This could be related to the chronic nature of TBM which may lead to vasculitis (likely proliferative lesions as seen in pathology studies). In our series, four of the five (80%) patients had vasculitis at follow-up at an average interval of 4.75 months (one patient demonstrated vasculitis at 16 months of follow-up while on antituberculous therapy for the entire duration). The initial risk for acute infarcts is attributed to vasospasm and less commonly to vascular thrombosis; while, infarcts in the later stage of the disease are attributed to proliferative lesions causing luminal compromise due to thickening of the vessel wall.[11],[15] In our study, patients with both acute and chronic infarcts had vasculitis involving the larger proximal vessels supplying the involved territories. Vessels of posterior circulation were found to be more affected than those of the anterior circulation. This finding is also supported by autopsy data which shows a similar finding with 100% involvement of vessels of the posterior circulation.[7]

Previous studies have described the presence of meningitis, tuberculomas, and exudates along with the basal cisterns and Sylvian fissures as predictors for the development of infarcts[5],[16],[17] and thus possible vasculitis. In our study, patients with tuberculomas either along the basal cisternal spaces or involving the parenchyma with brain stem edema were more likely to be clinically unstable with the presence of vasculitis in five of the six (83%) patients. Leptomeningeal enhancement was seen in all six patients with vasculitis. Leptomeningeal enhancement and basal cisternal tuberculoma were not observed in any of the patients without vasculitis. Thus, leptomeningeal enhancement and basal cisternal tuberculomas may predict the development of vasculitis which in turn likely predisposes patients to the development of acute infarcts.

This study has multiple limitations which include a lack of VWI both during the initial presentation and on follow-up. Only one of the five patients who underwent VWI during the initial presentation returned for follow-up imaging due to persistent symptoms. Other patients had significant clinical improvement on follow-up. VWI in the other five clinically unstable patients were avoided during the initial presentation. This has a limited our assessment of the temporal evolution of vasculitis.


  Conclusion Top


Intracranial vasculitis is observed in patients with TBM and can be documented with MR-based VWI. Vasculitis in TBM is more frequently seen in patients with severe disease at presentation and it may have some association with meningeal enhancement and the presence of tuberculomas along the basal cisterns. The presence of vasculitis in patients undergoing VWI during their follow-up visit while still on treatment may suggest the development of vasculitis over a prolonged duration and in the authors' opinion would probably explain the development of late-onset infarcts. VWI can therefore be used for follow-up of patients with TBM to identify vasculitis and thus probably predict the possibility of development of new infarcts.

Ethical clearance

The study was cleared by the institutional review board (IRB Min No: 10372).

Financial support and sponsorship

This study was funded by the “Fluid research grant” of Christian Medical College, Vellore, India.

Conflicts of interest

There are no conflicts of interest.



 
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