Adult Moyamoya: After the Diagnosis, Before the Event

Moyamoya disease is one of the few diseases of the brain's blood vessels in adult neurology where the diagnosis itself is rarely the contested question. The imaging, typically magnetic resonance angiography (MRA, an MRI sequence that maps the arteries themselves), shows the disease. The distal internal carotid arteries — the two main vessels running up the front of the neck that supply most of the brain — are stenosed (narrowed) or occluded (blocked); the small backup network at the base of the brain, the eponymous "puff of smoke" that gave the disease its name, is visible or it is not. The 2023 AHA/ASA scientific statement on adult moyamoya is the current adult reference, and it runs to the length its subject requires.¹ What it does not, and cannot, do is decide what should happen in the months between an adult moyamoya diagnosis and the next event. That decision is made, or not made, in the chart.

The Disease, Briefly

Moyamoya disease is a progressive, bilateral steno-occlusive arteriopathy (a disease that narrows and eventually blocks specific brain arteries on both sides), centered on the terminal portions of the internal carotid arteries and typically extending into the proximal middle and anterior cerebral arteries (the major branches that fan out across the side and front of the brain).¹ Disease progression recruits a fragile network of basal collaterals, the moyamoya vessels, which the brain enlarges to compensate for the loss of normal flow. They are visible on angiography (arterial imaging) as a hazy blush at the skull base. The Suzuki staging system, a six-stage angiographic grading scheme first described in 1969, remains the reference for tracking disease progression on imaging.²

Moyamoya syndrome, sometimes called quasi-moyamoya, describes a phenotypically similar vasculopathy associated with another condition: sickle cell disease, neurofibromatosis type 1, autoimmune disorders including antiphospholipid syndrome and systemic lupus, prior cranial irradiation, hyperthyroidism, or Down syndrome.¹ The distinction between disease and syndrome matters less for acute management than for the differential the chart should reflect: a finding of moyamoya pattern is not, on its own, a diagnosis.

The natural history splits along an age axis. In children, moyamoya tends to present ischemically, with strokes caused by blocked blood flow rather than bleeding, often as transient ischemic attacks (TIAs, brief stroke-like episodes that resolve), recurrent strokes, or cognitive decline. In adults, presentation is bimodal: both ischemic events and hemorrhagic events (strokes caused by bleeding into or around the brain) occur, with hemorrhagic presentation more common among adults than children and the East-Asian and Western adult cohorts skewing in different directions on the ratio.¹³ The adult disease is the one that reaches medico-legal review, and the analytical work is adult-specific. Pediatric data, including a substantial literature on indirect revascularization, does not transfer cleanly upward and should not be treated as if it does.

One geography note, stated once. The strongest evidence base in moyamoya derives from East Asian populations, where the RNF213 p.R4810K susceptibility variant (a genetic risk allele common in those populations and rare elsewhere) is widespread, and the disease is substantially more prevalent than in Western populations.¹³ The Western adult is genetically and epidemiologically distinct. That distinction does not invalidate the data; it informs the register at which it should be applied.

Ischemic and Hemorrhagic Are Not the Same Disease

The single most consequential failure of analysis in adult moyamoya cases is treating the disease as a unified entity for purposes of management. It is not.

Ischemic-type adult disease produces TIAs, watershed infarcts (strokes in the boundary zones between two arteries' supply territories, where flow is most precarious), and progressive cognitive change driven by chronic hypoperfusion (chronically reduced blood flow to the brain). Management questions center on hemodynamic compromise (inadequate blood-flow reserve) and whether perfusion can be augmented before the next event.

Hemorrhagic-type adult disease produces bleeds into the brain's fluid spaces (intraventricular) or directly into the brain tissue (intraparenchymal), often from rupture of the fragile collateral vessels themselves or from associated aneurysms (focal outpouchings of an artery wall that can leak or rupture). Management questions center on rebleeding risk and the role of bypass surgery — surgically routing a new source of blood flow into the brain — in lowering it. The Japan Adult Moyamoya Trial (JAM), the trial that anchors current adult bypass recommendations in hemorrhagic-type disease, was conducted exclusively in this population for that reason.⁴

The treatment evidence diverges. The blood-pressure plan diverges. The antiplatelet decision diverges. Any adult case that has not classified the phenotype before opining on management has skipped the step that determines which evidence applies.

The Decision Space After the MRA

Once the diagnosis is made, the chart has six decisions to document. Their absence is itself an analytical fact.

• Referral. Adult moyamoya is uncommon enough that most general neurology practices see one or two cases in a career. The 2023 scientific statement identifies management at a center with cerebrovascular surgical capability as relevant to outcomes.¹ What the record should show is the conversation: was referral offered, accepted, declined, deferred? A diagnosis named in a discharge summary that does not appear again until the index event is its own kind of record.
• Hemodynamic assessment. Cerebrovascular reserve (CVR) is the brain's flow headroom: its capacity to dilate its arteries when challenged with a vasodilatory stimulus, typically the drug acetazolamide or a brief rise in inhaled carbon dioxide (hypercapnia). It is measured by perfusion imaging (scans that quantify blood flow into different parts of the brain) or BOLD-CVR (a specialized MRI technique). Hemodynamic compromise (reduced or exhausted reserve) is a recognized risk factor for recurrent ischemic events in moyamoya, and a JAM supplementary analysis extended that signal to subsequent hemorrhage in hemorrhagic-type disease as well.⁵ The PIRAMD scoring system, a published tool that combines prior infarcts, reactivity (CVR), and angiographic findings into a single severity score, operationalizes that data into a graded surgical-candidacy framework.⁶ The analytical point is not that any single test predicts the next event with precision. It is that the absence of hemodynamic data from a chart in which revascularization was deferred is itself a finding: the deferral was made without information the field treats as relevant.
• Antiplatelet therapy in ischemic-type disease. Both the 2023 AHA/ASA scientific statement and the 2021 Japanese guidelines describe antiplatelet therapy (drugs such as aspirin that reduce clot formation) as reasonable rather than recommended.¹⁷ The cautious register is earned. A 2023 systematic review and meta-analysis pooling 16,186 patients across nine studies found that antiplatelet therapy reduced the risk of hemorrhagic stroke and did not significantly reduce the risk of ischemic stroke or improve functional independence.⁸ An ischemic-type adult moyamoya patient on aspirin is not on aspirin because the evidence shows aspirin prevents the next ischemic event in this disease. The chart that says otherwise has misread what was prescribed. Anticoagulation (stronger blood-thinning therapy of the warfarin or DOAC class) in any moyamoya patient deserves specific scrutiny; it is not the antithrombotic the disease asks for.
• Blood-pressure management in hemorrhagic-type disease. The literature on rebleeding in adult hemorrhagic moyamoya is thinner than the BP literature in non-moyamoya intracerebral hemorrhage. The JAM prespecified subgroup analysis identified posterior hemorrhage as a particularly high-risk site for rebleeding.⁹ What the record should show is whether the post-discharge BP plan reflected the diagnosis already known, or read as generic post-hemorrhage boilerplate.
• Revascularization. The options are direct, indirect, or combined. The direct procedure, most commonly STA–MCA bypass, surgically connects a scalp artery (the superficial temporal artery, STA, which runs in front of the ear) to a surface artery on the brain (a branch of the middle cerebral artery, MCA), creating an immediate new flow channel. The indirect procedure, encephaloduroarteriosynangiosis (EDAS) and its variants, lays vascular scalp tissue against the surface of the brain so new vessels grow into the cortex over weeks to months. Combined approaches do both. JAM established benefit of bilateral extracranial-intracranial direct bypass (bypass on both sides of the brain, from outside the skull to inside) over conservative management in adult hemorrhagic moyamoya: the composite endpoint of recurrent bleeding, completed stroke, or crescendo TIA (clusters of worsening transient attacks) was lower in the surgical arm.⁴ The trial enrolled 80 patients in Japan; subsequent prespecified analyses have refined the patient subset in whom benefit is most pronounced.⁵⁹ For ischemic-type adult disease, the evidence is observational. The 2024 Lim analysis is a recent observational study stratifying bypass outcomes by onset type, but a definitive randomized controlled trial in this population does not exist.¹⁰
• Surveillance. Imaging interval. Symptom-recognition plan given to the patient. Defined return criteria. A chart that stops at the diagnosis has stopped doing the work the diagnosis requires.

The Surveillance the Diagnosis Requires

Surveillance in adult moyamoya is not optional, and it is not generic stroke-clinic follow-up. The disease progresses at a rate the literature has characterized but cannot predict in the individual patient. MRA at intervals tied to phenotype and stage; perfusion or CVR studies when hemodynamic data drives a treatment question; digital subtraction angiography (DSA, the catheter-based gold-standard arterial study, in which contrast dye is injected through a catheter threaded from the groin) when the surgical question is live.¹ The choice of modality is less analytically interesting than whether the interval was tied to the disease at all. A patient told to "follow up as needed" after a moyamoya diagnosis has been managed as if the diagnosis were incidental.

What the Literature Will and Will Not Carry

Three calibrations matter.

The JAM trial established a benefit of bilateral extracranial-intracranial direct bypass in adult hemorrhagic moyamoya. It did so in a single multicenter trial of 80 patients in Japan, with the prespecified site and hemodynamic analyses since published narrowing the conditions under which the benefit is most pronounced.⁴⁵⁹ It is not a global mandate. It is a defensible recommendation in the right adult patient, and its weight on cross-examination depends on whether the case at hand resembles the JAM cohort.

The 2023 AHA/ASA scientific statement is the current adult reference. It carries the antiplatelet recommendation at the language the evidence supports, reasonable rather than indicated, and notes that no specific recommendation exists for cilostazol (an antiplatelet alternative to aspirin commonly used in East Asian practice) over alternatives.¹

The adult ischemic-type bypass evidence is observational. The 2024 Lim analysis stratifies outcomes by onset type and is a recent observational entry, but a definitive randomized controlled trial does not exist.¹⁰ An expert opinion that engages this gap is more durable than one that elides it.

Where the Management Goes Wrong

The cases that reach review tend to fail in a small number of recurring ways.

• Diagnosis named, referral never made. The MRA reads positive, the impression line reads "moyamoya pattern," and the chart never returns to it. The next entry is the index event.
• Watchful waiting without hemodynamic data. The decision to defer revascularization is defensible on the right data and indefensible on no data. A chart that documents "stable on conservative management" without a perfusion study, a CVR measurement, or a PIRAMD-equivalent assessment has documented the conclusion without the input.
• Hemorrhagic-type disease managed without engagement of the JAM evidence. A chart that does not document the bypass conversation in an adult hemorrhagic moyamoya patient has skipped the conversation the literature now expects.
• Ischemic-type management that treats antiplatelet therapy as if it prevented ischemic events. The literature does not support that expectation. A chart that documents aspirin "for stroke prevention" in this disease has misread the agent.
• Anticoagulation started by another service. A non-stroke admission, an atrial fibrillation diagnosis (a common heart-rhythm disorder for which anticoagulation is often prescribed), a DVT prophylaxis order (preventive blood-thinning for clots in the legs), and no documented reassessment of bleeding risk in a patient whose underlying vasculopathy is fragile by definition.
• Intracranial stenting offered as a substitute for surgical revascularization. Stenting (the placement of a metal-mesh tube inside a narrowed brain artery to hold it open) has been studied in moyamoya, and the literature is consistent that it fails to prevent ischemic events in this disease and does not halt disease progression.¹ An opinion that turns on a stenting decision should know this.
• No surveillance plan. The patient is given the diagnosis and discharged into a calendar that does not account for it.

These are not separate failure modes. They compound. A diagnosis without referral produces a follow-up plan without surveillance; a follow-up plan without surveillance produces a chart without hemodynamic data; a chart without hemodynamic data produces a deferral decision without a defensible basis.

Reading an Adult Moyamoya Case in Context

A defensible review of a case where adult moyamoya is central to the evidence, plaintiff or defense, works through a small set of specific questions.

• Was the phenotype, ischemic or hemorrhagic, classified, or was the disease treated as a unified entity?
• What does the referral pathway show, from the date of diagnosis forward? If referral was offered and declined, the documentation of the conversation matters.
• Was cerebrovascular reserve assessed before any deferral of revascularization, or was deferral made without it?
• For ischemic-type disease: what antiplatelet decision was documented, with what reasoning, and at what level of expectation? Was anticoagulation considered or started, and was the decision revisited against the diagnosis?
• For hemorrhagic-type disease: what does the BP record between diagnosis and event show, and was the plan tied to the diagnosis the patient carried?
• Was revascularization decided, deferred, or unaddressed? If deferred, against what data?
• What was the surveillance plan, in dates and modalities, and did it match the disease or the clinic's default?
• Does the index event sit inside a recognized failure pattern, or outside it?

Most cases resolve once these elements are placed in order. Some that look strong on the complaint dissolve against a chart documenting a careful conversation, a refused referral, and surveillance the patient missed. Others that look strong on the defense collapse against a chart in which a moyamoya diagnosis was named once and never engaged.

The MRA shows the disease. The chart shows what was done with it. In adult moyamoya cases, the analytical work lives in the second.

References

Footnotes

1. Gonzalez NR, Amin-Hanjani S, Bang OY, et al. Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke. 2023;54(10):e465–e479. doi:10.1161/STR.0000000000000443 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰

2. Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20(3):288–299. doi:10.1001/archneur.1969.00480090076012 ↩

3. Uchiyama S, Fujimura M. Adult Moyamoya Disease and Moyamoya Syndrome: What Is New? Cerebrovasc Dis Extra. 2024;14(1):86–94. doi:10.1159/000540254 ↩ ↩²

4. Miyamoto S, Yoshimoto T, Hashimoto N, et al. Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya Trial. Stroke. 2014;45(5):1415–1421. doi:10.1161/STROKEAHA.113.004386 ↩ ↩² ↩³

5. Takahashi JC, Funaki T, Houkin K, et al. Impact of cortical hemodynamic failure on both subsequent hemorrhagic stroke and effect of bypass surgery in hemorrhagic moyamoya disease: a supplementary analysis of the Japan Adult Moyamoya Trial. J Neurosurg. 2021;134(3):940–945. doi:10.3171/2020.1.JNS192392 ↩ ↩² ↩³

6. Ladner TR, Donahue MJ, Arteaga DF, et al. Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging. J Neurosurg. 2017;126(2):495–503. doi:10.3171/2015.11.JNS15562 ↩

7. Fujimura M, Tominaga T, Kuroda S, et al. 2021 Japanese Guidelines for the Management of Moyamoya Disease: Guidelines from the Research Committee on Moyamoya Disease and Japan Stroke Society. Neurol Med Chir (Tokyo). 2022;62(4):165–170. doi:10.2176/jns-nmc.2021-0382 ↩

8. Liu T, Qin M, Xiong X, et al. Benefits and risks of antiplatelet therapy for moyamoya disease: a systematic review and meta-analysis. Front Neurol. 2023;14:1132339. doi:10.3389/fneur.2023.1132339 ↩

9. Takahashi JC, Funaki T, Houkin K, et al. Significance of the Hemorrhagic Site for Recurrent Bleeding: Prespecified Analysis in the Japan Adult Moyamoya Trial. Stroke. 2016;47(1):37–43. doi:10.1161/STROKEAHA.115.010819 ↩ ↩² ↩³

10. Lim YC, Lee E, Song J. Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type. JAMA Netw Open. 2024;7(6):e2415102. doi:10.1001/jamanetworkopen.2024.15102 ↩ ↩²