Pediatric Moyamoya Syndrome Secondary to Tuberculous Meningitis

Abstract

Objectives

Tuberculosis is uncommon in the United States and a rare cause of meningitis in children with severe neurologic consequences. Tuberculous meningitis (TBM) is an even rarer cause of moyamoya syndrome with only a handful of cases previously reported.

Methods

We report the case of a female patient who initially presented at 6 years of age with TBM and developed moyamoya syndrome requiring revascularization surgery.

Results

She was found to have basilar meningeal enhancement and right basal ganglia infarcts. She was treated with 12 months of antituberculosis therapy and 12 months of enoxaparin and maintained on daily aspirin indefinitely. However, she developed recurrent headaches and transient ischemic attacks and was found to have progressive bilateral moyamoya arteriopathy. At age 11 years, she underwent bilateral pial synangiosis for the treatment of her moyamoya syndrome.

Discussion

Moyamoya syndrome is a rare but serious sequalae of TBM and may be more common in pediatric patients. The risk of stroke may be mitigated by pial synangiosis or other revascularization surgeries in carefully selected patients.

PRACTICAL IMPLICATIONS

Pial synangiosis may help mitigate the risk of stroke in pediatric patients with moyamoya syndrome related to TBM.

Tuberculous meningitis (TBM) is rare in the United States but carries a high rate of morbidity and mortality. Characteristic findings on MRI include abscess, exudates, granulomas, periventricular infarcts, vasculitis, hydrocephalus, and basilar meningeal enhancement.¹ Moyamoya syndrome secondary to tuberculosis is rare with only a few cases reported, and management options are limited.² In this study, we describe the case of pediatric moyamoya syndrome secondary to TBM treated surgically with bilateral pial synangiosis 5 years after initial infection.

Case Report

The TBM infection in this case was previously reported in December 2019.³ In brief, a 6-year-old girl presented with a generalized tonic-clonic seizure and was initially discharged home after imaging findings of decreased perfusion were believed to be caused by postictal changes. She had no significant history other than a visit to Vietnam 2 years before presentation.

She returned 10 days later with recurrent fevers, headaches, and left-sided weakness. Lumbar puncture demonstrated lymphocytic pleocytosis with low glucose and elevated protein (white blood cells 252/mm³, 63% lymphocytes, total protein 87 mg/dL, glucose 39 mg/dL, and red blood cells 102/mm³). Repeat MRI of the brain and spine demonstrated dense exudates with enhancement of the basilar meninges, diffuse narrowing of the vessels of the circle of Willis, multiple punctate infarcts in the right middle cerebral artery (MCA) territory, and circumferential vessel wall thickening on vessel wall imaging (VWI).³ Although a T-SPOT test was nonconclusive and the CSF mycobacterium PCR test was negative, she was diagnosed with TBM and completed 12 months of antituberculosis therapy with a combination of rifampin, isoniazid, pyrazinamide, and ethionamide and steroids, enoxaparin, and daily aspirin. Serial MRI demonstrated tuberculomas that decreased in size over time (Figure 1), and steno-occlusive changes involving the supraclinoid internal carotid artery (ICA) and A1 segments, left greater than right, and severe segmental left P1 stenosis that worsened over time (Figure 1).

Figure 1. Serial MRI and MRA of the Brain Show Tuberculous Meningitis With Progressive Moyamoya Arteriopathy.

Arrows in upper MRI studies denote change in tuberculous lesion over time. Arrowheads in lower MRA studies denote changes in artery caliber over time. MRA = magnetic resonance angiography.

The patient was followed up at regular intervals with repeat MRI/MRA every 6 months for the first 18 months and then yearly. Nearly 5 years after initial presentation, she developed worsening headaches with 2 transient ischemic attacks (TIAs) several months apart. Follow-up MRI/MRA and cerebral catheter angiography demonstrated progressive steno-occlusive changes involving the supraclinoid ICA and circle of Willis with arterial phase lag in the right MCA territory and intrinsic external carotid artery (ECA)–ICA transdural collaterals in both hemispheres (Figure 2). Owing to this constellation of findings, she underwent indirect pial synangiosis bilaterally. Arachnoid and dural specimens were sent to pathology, and both showed negative results on acid-fast bacilli stain. At the most recent follow-up 6 months postoperatively, she was maintained on aspirin with interval engraftment of surgical vessels seen on MRI/MRA and no interval strokes or TIAs.

Figure 2. Progressive Moyamoya Arteriopathy With Transdural Collaterals.

(A–D) Digital subtraction angiography of the internal carotid arteries 16 months (A, B) and 58 months (C, D) after initial presentation of TBM demonstrated progressive stenosis of the right A1 and bilateral M1 segments (C, D, arrowheads). There was evidence of increased arterial phase lag in the right MCA territory and diminished opacification of the ACA/MCA watershed territories bilaterally on the 58-month DSA compared with that on the 16-month DSA. Note the interval appearance of the distal left ACA despite worsened stenosis of the left A1 segment, suggesting decreased competing flow from the contralateral ACA consistent with progressive right A1 segment arteriopathy. Overall, the constellation of findings is consistent with interval progressive moyamoya arteriopathy with the ACA/MCA watershed territories most at risk. (E) Frontal and lateral views of selective injections of the right ECA at 58 months demonstrated intrinsic EC-IC transdural collaterals in the right frontal and parietal lobes (arrows). (F) Frontal and lateral views of selective injections of the left ECA at 58 months demonstrated intrinsic EC-IC transdural collaterals in the left frontal lobe. There were no transdural collaterals seen on the 16-month DSA (not shown). (G) Intraoperative photograph demonstrates intrinsic EC-IC transdural collaterals from the dura entering the arachnoid. ACA = anterior cerebral artery; DSA = digital subtraction angiography; ECA = external carotid artery; EC-IC = external carotid to internal carotid; MCA = middle cerebral artery; TBM = tuberculous meningitis.

Discussion

TBM is rare in the United States and can be difficult to diagnose owning to the nonspecificity of clinical presentation and low sensitivity of laboratory studies.⁴ Neuroradiographic studies can be particularly helpful in diagnosis, and serial VWI may be a helpful adjunctive tool.³ Predominantly basilar meningeal enhancement on MRI with thick exudates and tuberculomas are often seen (Figure 1). Cerebrovascular pathology in TBM results from close approximation to, or immersion in, the inflammatory exudates or granulomatous tissue, generating local inflammation, vasospasm, and/or intimal thickening.⁵ Therefore, patients with thick and focal exudates may be at risk of infarction in the associated vascular territory, commonly the basal ganglia.

Moyamoya syndrome secondary to TBM is rare² but has been associated with other infectious etiologies.⁶ In 1966, Lehrer⁷ described the angiographic triad of intracranial vascular findings in TBM including (1) wide sweeping pericallosal arteries; (2) narrowing of the supraclinoid ICA; and (3) narrowed small-sized and medium-sized vessels with early draining veins. In our patient, we found narrowing of the supraclinoid ICA and circle of Willis including the A1, M1, and P1 segments bilaterally (Figure 2).

In the absence of ventriculomegaly, we did not see sweeping pericallosal arteries. We did see prominent ECA-ICA transdural and leptomeningeal collaterals, which progressed over the course of 5 years consistent with moyamoya syndrome. Owing to these angiographic findings with evidence of progressive moyamoya arteriopathy and recurrent TIAs, our patient was treated surgically with bilateral pial synangiosis for revascularization.

In rare cases, TBM may lead to moyamoya syndrome with TIAs and strokes many years after initial presentation. As a result, patients with cerebral arteriopathy after TBM should be followed up closely with serial neuroimaging. We follow-up with clinic visits and MRI/MRA every 6 months for the first 18 months and then yearly thereafter for at least 5 years or for any new neurologic symptoms. In cases of symptomatic moyamoya syndrome, surgical intervention may be a durable treatment option to prevent strokes in this population.

Appendix. Authors

Study Funding

The authors report no targeted funding.

Disclosure

The authors report no relevant disclosures. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.