Blurred by a “Puff of Smoke”—A Case-Based Review on the Challenging Recognition of Coexisting CNS Demyelinating Disease and Moyamoya Angiopathy
Abstract
1. Introduction
2. Case Presentation
2.1. Case 1: A 45-Year-Old Woman Was Referred to Our Cerebrovascular Department for MMA
2.2. Case 2: A 43 Years-Old Woman Was Evaluated in Our Institute Because of the Neuroradiological Finding of Unilateral MMA
3. Discussion
- -
- On one hand, it is indeed imperative to diagnose and promptly treat MMA at the early stages with antiplatelets and revascularization surgery, before irreversible stroke occurs.On the other hand, the definite diagnosis of MMA should not automatically exclude MS as a possible concomitant disease, especially considering the higher incidence of MS [6] and the role that autoimmune mechanisms potentially play in both these conditions. Thus, it may be reasonable to recommend CSF analysis and spine MRI in the diagnostic work-up of MMA, especially in the presence of atypical features, e.g., when MRI lesions are not exclusively located in the typical borderzone territories (‘watershed lesions’) and/or when their morphology may suggest a different etiology.
Case | Country/ Ethnicity | Age/Sex | Clinical Presentation | T2-w MRI White Matter Hyperintensities Location | Gadolinium Enhancement | Spine MRI | CSF OB | VEP | Other Tests | Angiogram Findings | Diagnosis | Any Clinical Stroke? | Treatment | FU | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
For MMA | For NMO | ||||||||||||||
[66] | Japan/ n.s. | 52/F | Blindness, sensory-motor impairment lower limbs, urinary retention | Not specified (Hemorrhage in right thalamus) Longitudinal thoracic spinal cord | Brain: − Spine: + | + | − | + | ANA (+ 1:80) Anti SS-A/B Ab (+) AQP4 Ab (+) ANCA (−) Anticardiolipin (−) | Bilateral ACA and MCA occlusion, bilateral MM network | MMA + NMO + Systemic sclerosis | Hemorrhage | n.s. (hemorrhagic) | High dose i.v. corticosteroid pulse | 4 month |
[67] | Hong Kong/East Asian | 62/F | Gait impairment to tetraparesis and sensory impairment | Brain: − Longitudinal cervico-thoracic (C2-T3) lesions | Spine: n.s. | + | n.s. | + | Anti SS-A Ab (+) AQP4 Ab (+) ANA (−) | Bilateral ICAD and MCA occlusion, bilateral MM network | MMA + NMO | n.s. | n.s. | High dose i.v. corticosteroid pulse, followed by oral tapering and azathioprine, followed by cyclophosphamide | 8 month |
[26] | China/ n.s. | 43/F | Left sensory impairment | Brain: centrum semiovale + DWI restriction in right thalamus, hemosiderin deposition in left basal ganglia Thoracic spinal cord | Brain: n.s. Spine: n.s. | + | n.s. | + | AQP4 Ab (+) | Bilateral ACA and MCA, right PCA and right ICAD stenosis, bilateral MM network | MMA + NMO | Hemorrhagic and ischemic | (hemorrhagic) Antiplatelet | I.v. and oral corticosteroids, azathioprine | 6 month |
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene (Transcript) | Nucleotide Change | Aminoacid Change | ACMG Class * | Disease (OMIM) |
---|---|---|---|---|
RNF213 (NM_001256071.3) | c.12092T>C | p.Ile4031Thr | III (VUS) | Moyamoya (*607151) |
NOTCH3 (NM_000435.3) | c.2738C>T | p.Pro913Leu | III (VUS) | Cerebral arteriopathy (*600276) |
COL4A1 (NM_0018450.6) | c.1588C>T | p.Pro530Ser | III (VUS) | Microangiopathy and leukoencephalopathy, pontine, autosomal dominant (*618564) |
JAK1 (NM_002227.4) | c.1513G>A | p.Gly505Ser | III (VUS) | Autoinflammation, Immune dysregulation (*618999) |
Case | Country/Ethnicity | Age/ Sex | Clinical Presentation | T2-w MRI White Matter Hyperintensities Location | Gadolinium Enhancement | Spine MRI | CSF OB | VEP | Other Tests | Angiogram Findings | Diagnosis | Any Clinical Stroke? | Treatment | FU | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
For MMA | For MS | ||||||||||||||
[6] (case 3) | US/ n.s. | 44/F | Intermittent left hemiparesis | Multiple subcortical lesions (n.s.) | n.s. | − | + | − | n.s. | Left ICA occlusion, severe right ICAD stenosis, bilateral MM network | MMA + MS | Ischemic stroke | Bilateral bypass surgery, Aspirin | b-interferon, glatiramer acetate, high dose i.v. corticosteroids | 6 month |
[6] (case 9) | US/ n.s. | 31/F | Limb numbness and weakness, memory impairment | Multiple subcortical lesions (n.s.) | n.s. | n.s. | n.s. | n.s. | n.s. | Right MCA occlusion, R ACA stenosis | MMA + MS | n.s. | Right bypass surgery | n.s. | 18 month |
[7] (case 2) | US/ n.s. | 44/M | Right hemiparesis; impaired vision | Periventricular | Brain: − | n.p. | − | + | ANA (+)—ENA (−) | Left ACA, MCA and PCA stenosis | MMA mimicking/ associated with MS (discussion not conclusive) | TIA | Aspirin + Clopidogrel | b-interferon (stopped after MMA evidence) | n.s. |
[8] | China/ n.s. | 42/M | Right hemiparesis, speech impairment | Cervical spinal cord; Frontal, parietal, temporal lobe | Brain: + Spine: + | + | + | + | Anti-b2-glycoprotein I IgA (++) | Bilateral ICAD and right MCA occlusion; Left ACA, MCA, PCA stenosis | MMA + MS | Ischemic stroke (during steroid administration) | Aspirin + Clopidogrel; bilateral bypass surgery | High dose i.v. methylprednisolone | 3 month |
[9] | US/ Caucasian | 57/F | Episodic gait dysfunction; feet paresthesias; myelopathic signs | Cervical and thoracic spinal cord; bilateral frontal lobes; right pons; right cerebellum | Brain: spotty + Spine: − | + | + | NA | ANA (+ 1:80) Ab anti AQP4 and anti MOG (−) Ab anti cardiolipin (−) | Bilateral MCA and ACA occlusion, MM network | MMA + MS | No | n.s. | n.s. | n.s. |
[10] | Saudi Arabia/ n.s. | 16/F | Left hemiparesis | Periventricular lesion | n.s. | n.s. | + | n.s. | n.s. | Bilateral steno-occlusion ICAs-MCAs, R-ACA and R-PCA stenosis, lentriculostriate network | MMA + MS | Ischemic stroke (2) | Aspirin; bilateral by-pass surgery | Interferon beta and steroids | n.s. |
Our Case 1 | Italy/ Caucasian | 45/F | Blurred vision and diplopia | Bilateral brainstem, left frontal and temporal lobe, right temporal lobe, cerebellar hemispheres, left periventricular region | Brain: | − | + | − | AntiAQP4 (−) Anti-ds DNA (+ 1:20) ANA-ENA-ANCA-Anti cardiolipin and beta2GP (−) | Bilateral MCAs and ACAs narrow, thick network of collateral vessels | MMA + MS | TIA | By-pass surgery, Aspirin | Corticosteroids Teriflunomide | 4 years |
Our Case 2 | Italy/ Caucasian | 43/F | Left hemi-anesthesia (transient, recurring) | Bilateral supratentorial periventricular with corpus callosum involvement, left cerebellar hemisphere; bulbospinal tract; cervical spine | Brain: − Spine: − | + | + | − | AntiAQP4 (−) Anti-ds DNA-ANA-ENA-ANCA-Anti cardiolipin and beta2GP(−) G20210A Factor II and MTHFRC1677T (heterozigosis) Total body PET (−) | Left MCA and distal ICA steno-occlusion, MM network | MMA + MS | no | Aspirin | Dimethylfumarate Glatiramer acetate Teriflunomide | 8 years |
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Canavero, I.; Rifino, N.; Antozzi, C.; Caldiera, V.; Colombo, E.; Carrozzini, T.; Ganci, G.; Ferroli, P.; Acerbi, F.; Storti, B.; et al. Blurred by a “Puff of Smoke”—A Case-Based Review on the Challenging Recognition of Coexisting CNS Demyelinating Disease and Moyamoya Angiopathy. Int. J. Mol. Sci. 2025, 26, 5030. https://doi.org/10.3390/ijms26115030
Canavero I, Rifino N, Antozzi C, Caldiera V, Colombo E, Carrozzini T, Ganci G, Ferroli P, Acerbi F, Storti B, et al. Blurred by a “Puff of Smoke”—A Case-Based Review on the Challenging Recognition of Coexisting CNS Demyelinating Disease and Moyamoya Angiopathy. International Journal of Molecular Sciences. 2025; 26(11):5030. https://doi.org/10.3390/ijms26115030
Chicago/Turabian StyleCanavero, Isabella, Nicola Rifino, Carlo Antozzi, Valentina Caldiera, Elena Colombo, Tatiana Carrozzini, Giuseppe Ganci, Paolo Ferroli, Francesco Acerbi, Benedetta Storti, and et al. 2025. "Blurred by a “Puff of Smoke”—A Case-Based Review on the Challenging Recognition of Coexisting CNS Demyelinating Disease and Moyamoya Angiopathy" International Journal of Molecular Sciences 26, no. 11: 5030. https://doi.org/10.3390/ijms26115030
APA StyleCanavero, I., Rifino, N., Antozzi, C., Caldiera, V., Colombo, E., Carrozzini, T., Ganci, G., Ferroli, P., Acerbi, F., Storti, B., Boncoraglio, G. B., Potenza, A., Pollaci, G., Gorla, G., Ciceri, E., De Marco, P., Gatti, L., & Bersano, A. (2025). Blurred by a “Puff of Smoke”—A Case-Based Review on the Challenging Recognition of Coexisting CNS Demyelinating Disease and Moyamoya Angiopathy. International Journal of Molecular Sciences, 26(11), 5030. https://doi.org/10.3390/ijms26115030