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Table of Contents    
Year : 2020  |  Volume : 68  |  Issue : 3  |  Page : 660-664

Postcryptococcal Moyamoya Syndrome: Case Report and Review of Literature

Department of Neurology, Aster Medcity, Kochi, Kerala, India

Date of Web Publication6-Jul-2020

Correspondence Address:
Dr. Boby Varkey Maramattom
Department of Neurology, Aster Medcity, Kochi, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.288983

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 » Abstract 

There could be an association between cryptococcal meningitis and the later development of moyamoya syndrome. We performed serial clinical and radiological assessments in an immunosuppressed post-renal transplant patient who had previously suffered from cryptococcal meningitis and then went on to develop a moyamoya syndrome (MMS). We also performed a literature search and review of post-infectious MMS cases from 1976 to 2019. The clinical course and radiological findings were consistent with a diagnosis of MMS. After exclusion of other causes, accelerated MMS secondary to cryptococcal meningitis, developing over 1–2 months, was considered. Our observation adds further evidence to the concept of a post-infectious MMS. This report is the first to add fungal meningitis to the etiology of an MMS.

Keywords: Accelerated moyamoya, moyamoya syndrome, post cryptococcal moyamoya, post infectious intracranial vasculopathy, post meningitic moyamoya
Key Messages: Remote fungal meningitis could be a predisposing factor for Moya moya syndrome. Post infectious causes should always be considered in the etiology of Moya moya disease.

How to cite this article:
Maramattom BV. Postcryptococcal Moyamoya Syndrome: Case Report and Review of Literature. Neurol India 2020;68:660-4

How to cite this URL:
Maramattom BV. Postcryptococcal Moyamoya Syndrome: Case Report and Review of Literature. Neurol India [serial online] 2020 [cited 2020 Sep 22];68:660-4. Available from:

Moyamoya disease (MMD) is an idiopathic vasculopathy affecting the arteries of the anterior circulation at the base of the brain (internal carotid artery [ICA], middle cerebral artery [MCA], anterior cerebral artery [ACA]). The posterior circulation is often spared. As the disease progresses through various stages, thin collateral vessels that give the disease its name “moyamoya” (”puff of smoke”) are visualized at the base of the brain on digital subtraction angiography (DSA). In some cases, an underlying etiology is responsible for the same pattern, when it is referred to as the “moyamoya syndrome” (MMS). Post-infectious MMS has been described after meningitis following various organisms. We describe an unusual case of MMS that presented 3 years after cryptococcal meningitis in a renal transplant recipient.[1],[2],[3],[4],[5]

 » Case Report Top

A 36-year-old woman had undergone a live-related donor kidney transplantation three years earlier. She had been continuing triple immunosuppression with oral prednisolone, tacrolimus, and mycophenolate. Two months later, she had developed a severe headache and mild fever. After two weeks, she was seen in neurology and a lumbar puncture was performed. Cerebrospinal fluid (CSF) showed 30 cells with 95% lymphocytes, 71 mg/dL glucose, and 39 mg/dL protein. Indian ink stain showed cryptococcus and cryptococcal polymerase chain reaction (PCR) was also positive. Fungal culture grew Cryptococcus neoformans. She was started on liposomal amphotericin B and fluconazole for four weeks followed by oral maintenance fluconazole for one year. She was asymptomatic in 8 weeks and a repeat CSF examination and PCR/fungal culture were negative.

Two months earlier, she had presented to us with recurrent word finding difficulty. MRI showed critical stenosis at the left M1–M2 junction with a poor filling of the left M3 branches and a left subcortical rosary bead appearance of infarcts. She underwent a selective DSA of the left ICA which confirmed the findings. A repeat CSF examination was performed to rule out persistent low-grade central nervous system infection and was normal. Contrast MRI did not show any evidence of basal arachnoiditis. An MR aortogram was performed to look for systemic vasculitis but was essentially normal [Figure 1]. Despite double antiplatelet therapy (DAPT), she continued to have recurrent left MCA transient ischemic attacks (TIAs). She then underwent a left STA-MCA bypass surgery with the end to side anastomosis. Follow-up MRI on postoperative day (POD) 4 showed a patent left STA-MCA bypass [Figure 1].
Figure 1: (Panels A-C) Initial DWMRI, MRA, and DSA pre-op showing subcortical infarcts and distal M1–M2 segment stenosis. (Panel D) Normal MR aortogram. (Panels E and F) MRA, DWMRI on POD 22 showing a patent left STA-MCA anastomoses and a large opercular infarction. DSA: digital subtraction angiography, POD: postoperative day, STA-MCA: superficial temporal artery to middle cerebral artery

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Postoperatively, her blood pressures were persistently low (systolic blood pressure 100–110 mm Hg and diastolic blood pressure 50–60 mm Hg) and she was troubled with orthostatic transient ischemic spells. Repeat MRI on POD 22 showed progressive obliteration of the left MCA-M1 segment and a mild increase in the left opercular infarct. MRA had started demonstrating a slight irregularity of the right MCA proximal M1 segment by this time [Figure 1]. Her blood pressures were improved by midodrine 10 mg/day and oral/IV fluid supplementation to ~120/70 mm Hg. As the anastomosis was patent, single antiplatelet therapy was resumed.

1.5 months after the surgery, she noticed left leg weakness. An MRI on POD 46 showed a severe distal right ICA stenosis with an infarct in the territory of the recurrent artery of Heubner and lateral lenticulostriate arteries [Figure 2]. She was escalated to DAPT and low-molecular-weight heparin (LMWH), in spite of which she continued to have recurrent left-sided TIAs. As the left superficial temporal artery to middle cerebral artery (STA-MCA) bypass was just maturing, she was taken up for intracranial stenting with a drug-eluting stent after a multidisciplinary meeting with Nephrology and Neurosurgery, prior to a definitive STA-MCA bypass. Tacrolimus was substituted for everolimus in view of an initial suspicion of tacrolimus induced vasculopathy.[1] However, after creating and using a new diagnostic algorithm for MMD/MMS and ruling out other reasonable causes, we made a diagnosis of postcryptococcal MMS.
Figure 2: POD 46. (Panel A) DWMRI showing right RAH infarction. (Panels B and C) MRA and DSA showing proximal right MCA-M1 and ACA-A1 segment stenosis. ACA: anterior cerebral artery, DSA: digital subtraction angiography, MCA: middle cerebral artery. ICH, intracerebral hemorrhage, M. tuberculosis: Mycobacterium tuberculosis, SAH: subarachnoid hemorrhage

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On DSA, the right ICA was noted to be narrowed from the origin with a mean diameter of 3 mm. There was near occlusion of the right ACA-A1 segment and a 70% stenosis of the right proximal MCA-M1 segment with a mean diameter of 0.86 mm (distal MCA diameter 2.3 mm). The distal M3 branches were dilated, suggestive of an impaired cerebrovascular autoregulatory response. A 3 × 15 mm zotarolimus-eluting balloon mounted stent (Resolute onyx, Medtronic Corp) was passed over a wire into the right MCA and deployed. Post-stenting angiograms showed good MCA flow with a mean diameter of the right MCA of 3 mm. The cervical ICA diameter also increased from 3 to 5 mm. She was shifted to the ICU and ventilated. Three hours later, right-sided pupillary dilatation was noticed. An emergent CT showed a right parenchymal intracerebral hemorrhage with extensive subarachnoid extension. She underwent an immediate decompressive craniectomy, but continued to deteriorate postoperatively and expired after two days.

 » Discussion Top

MMD is a chronic idiopathic cerebral vasculopathy. It is characterized by a unilateral or bilateral steno-occlusive disease of the intracranial vasculature. This is associated with neovascular perforating vessels (”moyamoya vessels”) at the base of the brain. The anterior circulation is preferentially involved (terminal portion of the ICAs and a proximal portion of the MCAs and ACAs as well as the posterior communicating arteries). In earlier reports, the posterior circulation was thought to be spared; however, recent studies have shown posterior circulation involvement in 26–33% of patients with MMD.[2]

Suzuki characterized the clinical course of MMD into six stages in his seminal l969 paper.[3] In the stenosing phase, the anterior circulation progressively narrows and neovascularization with basal moyamoya vessels maintain perfusion. During the obliterative phase, even the neovascular network undergoes regression and the external carotid circulation finally takes over. The clinical manifestations are myriad and depend upon the vascular territory involved, stage of angiographic abnormalities, age group of presentation, and the response of the ischemic brain.[25],[26],[27] In children, the presentation is dominated by ischemic strokes, whereas there is a gradual shift to hemorrhagic strokes in adults. Hemorrhages can be intraventricular, intraparenchymal, or subarachnoid and are likely because of rupture of fragile collateral vessels associated with MMD or aneurysmal rupture. In MMD, arteriosclerotic changes are strikingly absent in the occlusive segments. It is a combination of smooth muscle hyperplasia and luminal thrombosis that induce luminal narrowing. The arterial media is compromised with the irregular elastic lamina. When these vessels collapse and thrombose, ischemic symptoms dominate the clinical presentation. The basal collateral network comprises dilated perforating arteries, both pre-existing and neovascular vessels. The vastly increased flow through these fragile vessels leads to stress-induced elastic lamina fragmentation, thinning of the media and the formation of microaneurysms. Moreover, aneurysms can form at major arteries (around the circle of Willis) or other distal arteries (the anterior or posterior choroidal artery). Any of these aneurysms can rupture with devastating consequences.

A genetic predisposition to MMD has been recently discovered. A gene locus for autosomal dominant MMD has been discovered in RNF213 in the 17q25-ter region among East Asian populations.[4] This mutation in this region affects TIMP-2 (tissue inhibitor of matrix metalloproteinase type 2) which has an important role in extracellular- matrix remodelling and angiogenesis.[4]

MMS is a secondary vasculopathy that has been described in association with multiple conditions including intracranial infections such as meningitis.[5] A Pubmed search for the last 43 years revealed 22 articles with a total number of 42 subjects, pertaining to MMS secondary to intracranial infection [Table 1]. The majority occurred in children 26/42 (62%). Viral infections accounted for the majority (66%) of MMS with most cases being attributed to HIV infection (62%). Bacterial meningitis accounted for 14/42 (33%). There were no cases reported with fungal meningitis. Most cases occurred within a few months to years after the primary infection. In rare instances, MMD was detected decades after the primary infection. Similar to MMD, the outcome of MMS was variable ranging from stable disease to severe disability and death.
Table 1: Review of the postinfective cases

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Although the pathophysiology of postinfectious MMS is unclear, a number of mechanisms have been proposed. These include an inflammatory vasculitis elicited by the causative organism, an autoimmune vasculitis or reactive vasospasm. The intima of the blood vessel is thought to be infiltrated and elevated by a polymorphonuclear response. This leads to intimal narrowing, proliferation of connective tissue, and smooth muscle muscles followed by the destruction of the internal elastic lamina causing stenosis/occlusion.[17] We did consider the possibility of postmeningitic basal arachnoiditis causing an MMS in our patient; however, a contrast MRI did not show any evidence of arachnoiditis.

Our case is unusual with respect to a few features. To the best of our knowledge, it is the first reported case of MMS following fungal meningitis, especially cryptococcus. Thus, this case report adds to the list of organisms that are capable of inducing an MMS after intracranial infection. It is also unusual with regard to the speed of progression. Within two months, our patient developed unilateral followed by bilateral intracranial vasculopathy. Most of the reported cases in the literature have presented with a slower progression of the disease.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 » References Top

Carson JM, Newman ED, Farber JL, Filippone EJ. Tacrolimus-induced thrombotic microangiopathy: Natural history of a severe, acute vasculopathy. Clin Nephrol 2012;77:79-84.  Back to cited text no. 1
Hishikawa T, Tokunaga K, Sugiu K, Date I. Assessment of the difference in posterior circulation involvement between pediatric and adult patients with moyamoya disease. J Neurosurg 2013;119:961-5.  Back to cited text no. 2
Suzuki J, Takaku A. Cerebrovascular “Moyamoya” disease: Disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20:288-99.  Back to cited text no. 3
Mineharu Y, Liu W, Inoue K, Matsuura N, Inoue S, Takenaka K, et al. Autosomal dominant moyamoya disease maps to chromosome 17q25.3. Neurology 2008;70:2357-63.  Back to cited text no. 4
Pinardi F, Stracciari A, Spinardi L, Guarino M. Postpneumococcal moyamoya syndrome case report and review of the postinfective cases. BMJ Case Rep 2013;2013. pii: bcr2012006726. doi: 10.1136/bcr-2012-006726.  Back to cited text no. 5
Stoeter P, Voigt K. Moyamoya syndrome of tuberculous cerebral arteritis. Rofo 1976;24:516-9.  Back to cited text no. 6
Kitahara M, Kaneko U, Fujiwara S, Suzuki J. A case showing angiographically moyamoya vessels combined with intracranial calcification. No Shinkei Geka 1986;14:367-72.  Back to cited text no. 7
Nakayama Y, Tanaka A, Nagasaka S, Ikui H. Intracerebral haemorrhage in a patient with moyamoya phenomenon caused by tuberculous arteritis: A case report. No Shinkei Geka 1999;27:751-5.  Back to cited text no. 8
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Takasugi H, Maemoto T, Kitazawa K, Honda A. [A case of down syndrome with moyamoya syndrome presenting extensive multiple cerebral infarction during measles infection]. No To Hattatsu 2000;32:39-43.  Back to cited text no. 12
Palacio S, Hart RG, Vollmer DG, Kagan-Hallet K. Late-developing cerebral arteropathy after pyogenic meningitis. Arch Neurol 2003;60:431-3.  Back to cited text no. 13
Czartoski T, Hallam D, Lacy JM, Chun MR, Becker K. Postinfectious vasculopathy with evolution to moyamoya syndrome. J Neurol Neurosurg Psychiatry 2005;76:256-9.  Back to cited text no. 14
Hammond CK, Shapson-Coe A, Govender R, van Toorn R, Ndondo A, Wieselthaler N, et al. Moyamoya syndrome in South African children with HIV-1 infection. J Child Neurol 2016;31:1010-7.  Back to cited text no. 15
Greco F, Castellano Chiodo D, Sorge A, Perrini S, Sorge G. Multiple arterial ischemic strokes in a child with moyamoya disease and Mycoplasma pneumonia infection. Minerva Pediatr 2006;58:63-8.  Back to cited text no. 16
Pugin D, Copin JC, Goodyear MC, Landis T, Gasche Y. Persisting vasculitis after pneumococcal meningitis. Neurocrit Care 2006;4:237-40.  Back to cited text no. 17
West SL, Newton RW, Baildam EM, Turner AJ, Arkwright PD. Recurrent hemiplegia associated with cerebral vasculopathy following third trimester maternal herpes zoster infection. Dev Med Child Neurol 2006;48:991-3.  Back to cited text no. 18
Galati V, Grilli E, Sallustio F, Petrosillo N. An adult HIV patient with unilateral moyamoya syndrome. Clin Neurol Neurosurg 2010;112:76-8.  Back to cited text no. 19
Javier F, Cardenas MD, Chapman K. Sydenham's chorea as a presentation of moyamoya disease. Semin Pediatr Neurol 2010;17:30-4.  Back to cited text no. 20
Pinardi F, Stracciari A, Spinardi L, Guarino M. Postpneumococcal moyamoya syndrome case report and review of the postinfective cases. BMJ Case Rep 2013;6;2013.  Back to cited text no. 21
Dhawan SR, Sahu JK, Vyas S, Singhi SC, Singhi PD. Pyogenic meningitis complicated with extensive central nervous system vasculitis and moyamoya vasculopathy. J Pediatr Neurosci 2018;13:343-5.  Back to cited text no. 22
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  [Table 1]


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