Moyamoya disease

Moyamoya disease

Moyamoya disease is a chronic, occlusive cerebrovascular disease, characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain.

These diagnostic criteria of the moyamoya disease, stated by the Research Committee on Spontaneous Occlusion of the Circle of Willis (moyamoya disease) in Japan, are well established and generally accepted as the definition of this rare entity. On the contrary to the diagnosis of definitive moyamoya disease, there is some confusion in the terminology and understanding of quasi-moyamoya disease; moyamoya disease in association with various disease entities, such as atherosclerosis, autoimmune diseases, Down syndrome, etc. Although the clinical management is not affected by these semantic distinctions, terminological confusion may interfere with the international collaboration of the clinical investigation of these rare conditions 1).

The perforating arteries in the basal ganglia and thalamus markedly dilate and function as an important collateral circulation, called as “moyamoya” vessels. The posterior cerebral artery are also involved in a certain subgroup of patients. Therefore, cerebral hemodynamics is often impaired especially in the frontal lobe, leading to transient ischemic attack (TIa) and cerebral infarction. Furthermore, the dilated, fragile moyamoya vessels often rupture and cause intracranial hemorrhage 2) 3).

Unknown etiology.

A study indicated a higher overall autoimmune disease prevalence in unilateral than in bilateral MMD. Unilateral MMD may be more associated with autoimmune disease than bilateral MMD. Different pathogenetic mechanisms may underlie moyamoya vessel formation in unilateral and bilateral MMD 4).

The p.R4810K mutation in RNF213 gene confers a risk of MMD, but other factors remain largely unknown. Mineharu et al. tested the association of gut microbiota with MMD. Fecal samples were collected from 27 patients with MMD, 7 patients with non-moyamoya intracranial large artery disease (ICAD) and 15 control individuals with other disorders, and 16S rRNA were sequenced. Although there was no difference in alpha diversity or beta diversity between patients with MMD and controls, the cladogram showed Streptococcaceae was enriched in patient samples. The relative abundance analysis demonstrated that 23 species were differentially abundant between patients with MMD and controls. Among them, increased abundance of Ruminococcus gnavus > 0.003 and decreased abundance of Roseburia inulinivorans < 0.002 were associated with higher risks of MMD (odds ratio 9.6, P = 0.0024; odds ratio 11.1, P = 0.0051). Also, Ruminococcus gnavus was more abundant and Roseburia inulinivorans was less abundant in patients with ICAD than controls (P = 0.046, P = 0.012). The relative abundance of Ruminococcus gnavus or Roseburia inulinivorans was not different between the p.R4810K mutant and wildtype. The data demonstrated that gut microbiota was associated with both MMD and ICAD 5).

The histopathological features of the middle cerebral artery (MCA) and superficial temporal artery (STA) from moyamoya disease (MMD) and their relationships with gender, age, angiography stage were explored. The causes and the clinical significance of vasculopathy of STA were also discussed. The clinical data and specimens of MCA and STA from 30 MMD patients were collected. Twelve samples of MCA and STA from non-MMD patients served as control group. Histopathological examination was then performed by measuring the thickness of intima and media, and statistical analysis was conducted. The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group. There was no significant pathological difference between the hemorrhage group and non-hemorrhage group, and between the males and females in MMD patients. Neither the age nor the digital subtraction angiography (DSA) stage was correlated with the thickness of intima in MCA and STA. MMD is a systemic vascular disease involving both intracranial and extracranial vessels. Preoperative external carotid arteriography, especially super-selective arteriography of the STA, benefits the selection of donor vessel 6).

Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya.

Computational fluid dynamics (CFD) analysis on eight patients (5 female, 3 male) with MMD treated by EDAS (encephalo-duro-arterio-synangiosis) between 2011 and 2012. All the eight patients presented with haemorrhage, with subsequent 4-12 month follow-up done using Magnetic Resonance Angiography (MRA) to capture auto-remodelling. Karunanithi et al. calculated percentage change in flow rate and pressure drop indicator (ΡDI) across the Left and Right ICA. Pressure drop indicator (PDI) is defined as the difference of pressure reduction within the carotid arteries, measured at post-op and follow up, using patient specific inflow rates. The measured percentage flow change and pressure reduction showed an increase at follow up for improved patients (characterised by angiography according to the method of Matsushima), who did not develop any complications after surgery. The inverse was observed in patients who were clinically classified as no change and retrogressed (according to the method of Matsushima) cases post-operation. This elucidates the findings of a new parameter that may well play a critical role as an assistive clinical decision making tool in MMD 7).

Artificial intelligence (AI) clustering was used to classify the articles into 5 clusters: (1) pathophysiology (23.5%); (2) clinical background (37.3%); (3) imaging (13.2%); (4) treatment (17.3%); and (5) genetics (8.7%). Many articles in the “clinical background” cluster were published from the 1970s. However, in the “treatment” and “genetics” clusters, the articles were published from the 2010s through 2021. In 2011, it was confirmed that a gene called Ringin protein 213 (RNF213) is a susceptibility gene for moyamoya disease. Since then, tremendous progress in genomictranscriptomics, and epigenetics (e.g., methylation profiling) has resulted in new concepts for classifying moyamoya disease. The literature survey revealed that the pathogenesis involves aberrations of multiple signaling pathways through genetic mutations and altered gene expression 8).


1)

Fujimura M, Tominaga T. Diagnosis of moyamoya disease: international standard and regional differences. Neurol Med Chir (Tokyo). 2015 Mar 15;55(3):189-93. doi: 10.2176/nmc.ra.2014-0307. Epub 2015 Feb 20. PubMed PMID: 25739428.
2)

Suzuki J, Takaku a: Cerebrovascular “moyamoya” disease. disease showing abnormal net-like vessels in base of brain. Arch Neurol 20: 288–299, 1969
3)

Kuroda S, Houkin K: Moyamoya disease: current concepts and future perspectives. Lancet Neurol 7: 1056–1066, 2008
4)

Chen JB, Liu Y, Zhou LX, Sun H, He M, You C. Increased prevalence of autoimmune disease in patients with unilateral compared with bilateral moyamoya disease. J Neurosurg. 2015 Sep 25:1-6. [Epub ahead of print] PubMed PMID: 26406790.
5)

Mineharu Y, Nakamura Y, Sato N, Kamata T, Oichi Y, Fujitani T, Funaki T, Okuno Y, Miyamoto S, Koizumi A, Harada KH. Increased abundance of Ruminococcus gnavus in gut microbiota is associated with moyamoya disease and non-moyamoya intracranial large artery disease. Sci Rep. 2022 Nov 24;12(1):20244. doi: 10.1038/s41598-022-24496-9. PMID: 36424438.
6)

Sun SJ, Zhang JJ, Li ZW, Xiong ZW, Wu XL, Wang S, Shu K, Chen JC. Histopathological features of middle cerebral artery and superficial temporal artery from patients with moyamoya disease and enlightenments on clinical treatment. J Huazhong Univ Sci Technolog Med Sci. 2016 Dec;36(6):871-875. PubMed PMID: 27924520.
7)

Karunanithi K, Han C, Lee CJ, Shi W, Duan L, Qian Y. Identification of a hemodynamic parameter for assessing treatment outcome of EDAS in Moyamoya disease. J Biomech. 2015 Jan 21;48(2):304-9. doi: 10.1016/j.jbiomech.2014.11.029. Epub 2014 Nov 29. PubMed PMID: 25498370.
8)

Kuribara T, Akiyama Y, Mikami T, Komatsu K, Kimura Y, Takahashi Y, Sakashita K, Chiba R, Mikuni N. Macrohistory of Moyamoya Disease Analyzed Using Artificial Intelligence. Cerebrovasc Dis. 2022 Feb 1:1-14. doi: 10.1159/000520099. Epub ahead of print. PMID: 35104814.

Moyamoya Disease Diagnosis

Moyamoya Disease Diagnosis

Diagnosis of Moyamoya disease requires bilateral symmetrical stenosis or occlusion of the terminal portion of the internal carotid arterys (ICA)s as well as the presence of dilated collateral vessels at the base of the brain 1). (If unilateral, the diagnosis is considered questionable, 2) and these cases may progress to bilateral involvement).

Other characteristic findings include:

  1. stenosis/occlusion starting at the termination of ICA and at origins of ACA and MCA

  2. abnormal vascular network in the region of BG (intraparenchymal anastomosis).

  3. transdural anastomosis(rete mirabile), AKA “vault moyamoya.”Contributing arteries: anterior falcial, middle meningeal, ethmoidal, occipital, tentorial, STA

  4. moyamoya collaterals may also form from the internal maxillary artery via ethmoid sinus to the forebrain in the frontobasal region.

Work-up in suspected cases typically begins with a non-enhanced head CT. Up to 40% of ischemic cases have normal CT. Low-density areas (LDAs) may be seen, usually confined to cortical and subcortical areas (unlike atherosclerotic disease or acute infantile hemiplegia which tend to have LDAs in basal ganglia as well). LDAs tend to be multiple and bilateral, especially in the PCA distribution (poor collaterals), and are more common in children.

Magnetic resonance imaging for Moyamoya Disease Diagnosis.

In addition to helping to establish the diagnosis, angiography also identifies suitable vessels for revascularization procedures and unearths associated aneurysms. The angiography-related complication rate is higher than with atherosclerotic occlusive disease. Avoid dehydration prior to and hypotension during the procedure. Six angiographic stages of MMD are described by Suzuki and Takaku 3) that tend to progress up until adolescence and stabilize by age 20.

1 stenosis of suprasellar ICA, usually bilateral

2 development of moyamoya vessels at the base of the brain; ACA MCA & PCA dilated

3 increasing ICA stenosis & prominence of moya-moya vessels (most cases diagnosed at this stage); maximal basal moyamoya

4 entire circle of Willis and PCAs occluded, extracranial collaterals start to appear, moyamoya vessels begin to diminish

5 further progression of stage 4

6 complete absence of moyamoya vessels and major cerebral arteries.

Non-specific in the adult. Juvenile cases: high-voltage slow waves may be seen at rest, predominantly in the occipital and frontal lobes. Hyperventilation produces a normal buildup of monophasic slow waves (delta-bursts) that return to normal 20–60 seconds after hyperventilation. In >50%of cases, after or sometimes continuous with buildup is a second phase of slow waves (this characteristic finding is called “rebuild up”) which are more irregular and slower than the earlier waves, and usually, normalize in ≤10 minutes 4).

CBF is decreased in children with MMD, but relatively normal in adults. There is a shift of CBF from the frontal to the occipital lobes 5) probably reflecting the increasing dependency of CBF on the posterior circulation. Children with MMD have impaired autoregulation of CBF to blood pressure and CO2 (with more impairment of vasodilatation in response to hypercapnia or hypotension than vasoconstriction in response to hypocapnia or hypertension) 6). Xenon (Xe-133) CT can identify areas of low perfusion. Repeating the study after an acetazolamide challenge (which causes vasodilatation) evaluates the reserve capacity of CBF and can identify areas of “steal” which are at high risk of future infarction.

Ultrasound parameters are independently correlated with ipsilateral cerebral stroke in patients with Moyamoya disease (MMD). Ultrasound provides a new way to identify stroke in MMD patients. Future prospective cohort studies are needed to verify the clinical value of ultrasound in identifying patients with MMD at high risk of stroke 7).


1)

Smith ER, Scott RM. Surgical management of moyamoya syndrome. Skull Base. 2005; 15:15–26
2)

Nishimoto A. Moyamoya Disease. Neurol Med Chir. 1979; 19:221–228
3)

Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969 Mar;20(3):288-99. PubMed PMID: 5775283.
4)

Kodama N, Aoki Y, Hiraga H, et al. Electroencephalographic Findings in Children with Moyamoya Disease. Arch Neurol. 1979; 36:16–19
5)

Ogawa A, Yoshimoto T, Suzuki J, Sakurai J. Cerebral Blood Flow in Moyamoya Disease. Part 1. Correlation with Age and Regional Distribution. Acta Neurochir. 1990; 105:30–34
6)

Ogawa A, Nakamura N, Yoshimoto T, Suzuki J. Cerebral Blood Flow in Moyamoya Disease. Part 2. Autoregulation and CO2 Response. Acta Neurochir. 1990; 105:107–111
7)

Zheng S, Wang F, Cheng L, Li R, Zhang D, He W, Zhang W. Ultrasound parameters associated with stroke in patients with moyamoya disease: a logistic regression analysis. Chin Neurosurg J. 2022 Oct 11;8(1):32. doi: 10.1186/s41016-022-00300-5. PMID: 36221122.

Stroke in Moyamoya disease

Stroke in Moyamoya disease

Moyamoya disease (MMD) is an idiopathic disease with a progressive nature leading to recurrent stroke due to occlusion of the terminal internal carotid arteries 1).

A multi-center, nationwide survey for conservative treatment results was conducted in 2007 in Japan. The authors reported the annual stroke rate as 3.2% from the observation of 34 asymptomatic patients conservatively followed over 44 months. A hemodynamic disturbance was revealed to be a risk factor for newly developed stroke 2)

In a North American series, the rates of annual ischemic and hemorrhagic stroke rate were reported as 13.3% and 1.7%, respectively. Being female and smoking were risk factors for stroke development 3)

Cho et al. reported an annual stroke rate of 4.5% among 241 hemodynamically stable patients with MMD over 83 months. The annual stroke rate was higher in the hemorrhagic presentation group (5.7%) than in the ischemic presentation group (4.2%) or the asymptomatic group (3.4%). They found familial disease and thyroid disease to be risk factors affecting stroke occurrence 4). As for ischemic presenting MMD, 5.6% of the annual ischemic stroke rate also reported that posterior circulation involvement was a strong risk factor for ischemic stroke 5).

see Moyamoya disease diagnosis


It is necessary to find a non-invasive and effective approach to identify the occurrence of stroke.

Zheng et al. aimed to analyze the association between ultrasound parameters and ipsilateral cerebral hemisphere stroke in patients with moyamoya disease by logistic regression analysis.

In a retrospective case-control study, 88 patients with MMD (153 cerebral hemispheres) hospitalized in Beijing Tiantan Hospital, Capital Medical University from November 2020 to October 2021 were analyzed. According to the occurrence of stroke, the 153 cerebral hemispheres were divided into a stroke group and a non-stroke group. Clinical data and ultrasound parameters of the ipsilateral internal carotid arterysuperficial temporal arterymaxillary artery, and posterior cerebral artery were recorded. The ultrasound parameters were divided into four groups according to the interquartile range, and then they were compared between the stroke group and the non-stroke group. Those with significant differences were scored by multivariate logistic regression analysis.

There were 75 cerebral hemispheres (49.0%) in the stroke group and 78 cerebral hemispheres (51.0%) in the non-stroke group. Logistic regression analysis showed that the internal diameter of the internal carotid artery, peak systolic velocity of the internal carotid artery and peak systolic velocity of the posterior cerebral artery were independently correlated factors for stroke in patients with Moyamoya disease MMD. The fourth quartile group of the above three ultrasound parameters was taken as the reference group, and the odds ratio of the first quartile group were 11.679 (95% CI 2.918-46.749, P = 0.001), 19.594 (95% CI 4.973-77.193, P < 0.001), and 11.657 (95% CI 3.221-42.186, P < 0.001), respectively.

Ultrasound parameters are independently correlated with ipsilateral cerebral stroke in patients with Moyamoya disease (MMD). Ultrasound provides a new way to identify stroke in MMD patients. Future prospective cohort studies are needed to verify the clinical value of ultrasound in identifying patients with MMD at high risk of stroke 6).

Revascularization surgery for symptomatic MMD is considered the standard treatment for preventing further stroke 7) 8).


1)

Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969 Mar;20(3):288-99. doi: 10.1001/archneur.1969.00480090076012. PMID: 5775283.
2)

Kuroda S, Hashimoto N, Yoshimoto T, Iwasaki Y, Research Committee on Moyamoya Disease in Japan Radiological findings, clinical course, and outcome in asymptomatic moyamoya disease: results of multicenter survey in Japan. Stroke. 2007;38:1430–1435.
3)

Gross BA, Du R. The natural history of moyamoya in a North American adult cohort. J Clin Neurosci. 2013;20:44–48.
4)

Cho WS, Chung YS, Kim JE, Jeon JP, Son YJ, Bang JS, et al. The natural clinical course of hemodynamically stable adult moyamoya disease. J Neurosurg. 2015;122:82–89.
5)

Noh HJ, Kim SJ, Kim JS, Hong SC, Kim KH, Jun P, et al. Long term outcome and predictors of ischemic stroke recurrence in adult moyamoya disease. J Neurol Sci. 2015;359:381–388.
6)

Zheng S, Wang F, Cheng L, Li R, Zhang D, He W, Zhang W. Ultrasound parameters associated with stroke in patients with moyamoya disease: a logistic regression analysis. Chin Neurosurg J. 2022 Oct 11;8(1):32. doi: 10.1186/s41016-022-00300-5. PMID: 36221122.
7)

Fukui M. Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (‘moyamoya’ disease). Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg. 1997;99(Suppl 2):S238–240.
8)

Narisawa A, Fujimura M, Tominaga T. Efficacy of the revascularization surgery for adult-onset moyamoya disease with the progression of cerebrovascular lesions. Clin Neurol Neurosurg. 2009;111:123–126.

Moyamoya disease outcome

Moyamoya disease outcome

Moyamoya disease (MMD) is an idiopathic disease with a progressive nature leading to recurrent stroke due to occlusion of the terminal internal carotid arteries.


The effectiveness of surgery for long-term protection of cognitive function is unclear even if the initial surgical treatment may result in good neurological outcomes 1).


Brain functional and structural connectivity between the supplementary motor area and inferior frontal gyrus in the left hemisphere are damaged in moyamoya disease (MMD). These findings could be useful in the evaluation of disease progression and prognosis of MMD 2).


The disorder can lead to negative mood and stress, which, left unresolved, may increase adverse health outcomes. Yang et al. conducted a cross-sectional survey to examine the stress and mood of adults with moyamoya disease. Participants were recruited at a university hospital in SeoulKorea. Data were collected through questionnaires and review of participants’ electronic medical records. A total of 109 adult patients participated. Significant correlations were found between perceived stress, anxiety, and depression. Adults with moyamoya disease experience anxiety, depression, and stress-related to the risk of cerebral hemorrhage or ischemia, similar to patients with other cerebrovascular diseases. If uncontrolled, negative mood and stress can cause adverse health outcomes. Health professionals caring for patients with moyamoya disease should carefully observe patients’ stress and mood and develop interventions tailored to stages of the disease to help patients manage stress and mood. The study results provide baseline information for understanding the level of and the factors associated with stress and mood 3).


Pediatric Moyamoya disease patients have greater patency and a greater ability to establish good leptomeningeal collateral circulation (LMC) status than adult patients, and poor LMC status has a strong correlation with severe clinical symptoms and poor postoperative outcomes. LMC status may be an important factor in the differences in clinical characteristics and prognosis between pediatric and adult MMD patients 4).


Recurrent stroke after surgical revascularization is still a big issue for moyamoya disease (MMD).

Female, left-sided surgery, and edematous lesion were independent risk factors for postoperative TNEs; the left-sided surgery and edematous lesion were also independently associated with the severity of TNE. Although patients with postoperative TNEs had worse neurological status during the perioperative period, postoperative TNEs had no associations with worse mRS score at the time of discharge 5).


The outcome following surgery is very difficult to judge, and there is no standardised measurement to assess it. It is therefore important to know which approach for such patient is adequate.

Comparing to patients with acute idiopathic primary intraventricular hemorrhage (PIVH), patients with acute MMD-related PIVH have younger age, lower blood pressure, and better renal function. Moreover, patients with acute MMD-related PIVH have lower short-term mortality 6).


Sundaram et al., compared the long-term outcome of moyamoya patients treated conservatively to those who underwent RS.

A study population included all patients with moyamoya disease/syndrome from 2002 to 2012. The demographic, clinical characteristic and imaging details were reviewed. The outcome was obtained prospectively.

Of the 36 patients, 26 (72.2%) had MMD and 10 (27.8%) had moyamoya syndrome. The median age at onset of symptoms was 17.5 years (range, 10 months-55 years). Fifteen patients belonged to pediatric group and 21 were adults. All the pediatric patients had ischemic events at onset and 10 (47.6%) of the adults presented with hemorrhage. Twenty (55.6%) patients received conservative treatment and 16 (44.4%) underwent revascularization procedures. The median duration of follow-up was 28 months (range, 3-90 months). Three (18%) of the surgically treated patients had recurrent ischemic events on follow-up, but none of the conservatively treated patients had events. An excellent outcome (Modified Rankin Scale of ≤2) was seen in 12 (75%) surgically treated and 16 (94%) conservatively treated patients (p=0.17).

Compared to East Asians, our patients had a lower stroke recurrence rate and good functional outcome even with conservative treatment. Future studies should focus on clinical and imaging predictors of progression to select moyamoya patients for RS 7).


1)

Shim KW, Park EK, Kim JS, Kim DS. Cognitive Outcome of Pediatric Moyamoya Disease. J Korean Neurosurg Soc. 2015 Jun;57(6):440-4. doi: 10.3340/jkns.2015.57.6.440. Epub 2015 Jun 30. PMID: 26180613; PMCID: PMC4502242.
2)

Hu J, Li Y, Li Z, Chen J, Cao Y, Xu D, Zheng L, Bai R, Wang L. Abnormal brain functional and structural connectivity between the left supplementary motor area and inferior frontal gyrus in moyamoya disease. BMC Neurol. 2022 May 16;22(1):179. doi: 10.1186/s12883-022-02705-2. PMID: 35578209.
3)

Yang YS, Ryu GW, Yeom I, Shim KW, Choi M. Stress and Mood of Adults with Moyamoya Disease: A Cross-Sectional Study. Nurs Health Sci. 2020 Apr 26. doi: 10.1111/nhs.12729. [Epub ahead of print] PubMed PMID: 32336006.
4)

Liu ZW, Han C, Wang H, Zhang Q, Li SJ, Bao XY, Zhang ZS, Duan L. Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease. CNS Neurosci Ther. 2020 Jan;26(1):14-20. doi: 10.1111/cns.13130. Epub 2019 Apr 13. PubMed PMID: 31875482.
5)

Lu J, Zhao Y, Ma L, Chen Y, Li M, Chen X, Ye X, Wang R, Zhao Y. Predictors and clinical features of transient neurological events after combined bypass revascularization for moyamoya disease. Clin Neurol Neurosurg. 2019 Aug 29;186:105505. doi: 10.1016/j.clineuro.2019.105505. [Epub ahead of print] PubMed PMID: 31622898.
6)

Yu Z, Guo R, Zheng J, Li M, Wen D, Li H, You C, Ma L. Comparison of acute moyamoya disease-related and idiopathic primary intraventricular hemorrhage in adult patients. World Neurosurg. 2019 Jan 24. pii: S1878-8750(19)30167-6. doi: 10.1016/j.wneu.2019.01.070. [Epub ahead of print] PubMed PMID: 30685378.
7)

Sundaram S, Sylaja PN, Menon G, Sudhir J, Jayadevan ER, Sukumaran S, Sreedharan SE, Sarma S. Moyamoya disease: a comparison of long term outcome of conservative and surgical treatment in India. J Neurol Sci. 2014 Jan 15;336(1-2):99-102. doi: 10.1016/j.jns.2013.10.014. Epub 2013 Oct 16. PubMed PMID: 24183032.

Sickle Cell Disease Associated Moyamoya Syndrome

Sickle Cell Disease Associated Moyamoya Syndrome

Moyamoya syndrome (MMS) is a relatively uncommon vascular complication of sickle cell disease (SCD) characterized by progressive stenosis of the supraclinoid carotid arteries and development of typical collaterals


Sickle Cell Disease is associated with moyamoya-like changes on cerebral angiographic imaging in 43% of patients. Cerebral aneurysms,arteriovenous malformations, and dural arteriovenous fistulas (AVFs) have been described in association with SCD and moyamoya disease.


Moyamoya syndrome increases the risk of stroke in sickle cell disease

Collaborative management between hematology and neurosurgery offers effective strategies to reduce stroke risk in these patients.

Revascularization is associated with a significant reduction in stroke risk, both relative to prerevascularization rates and compared with medical management. According to these findings, surgical revascularization offers a safe and durable preventative therapy for stroke and should be pursued aggressively in this patient population 1).

A retrospective cohort study of medically managed vs surgically revascularized patients with moyamoya syndrome and sickle cell disease was conducted. Demographic data and outcomes including the number of prediagnosis, postdiagnosis, and postrevascularization strokes were collected. Risk factors for stroke were identified using a binary logistic regression model, and stroke rates and mortality between groups were compared.

Of the 29 identified patients, 66% were medically managed and 34% underwent surgical revascularization (50% direct and 50% indirect). Calculated stroke rates were 1 per 5.37 (medical management), 1 per 3.43 (presurgical revascularization), and 1 per 23.14 patient-years (postsurgical revascularization). There was 1 surgical complication with no associated permanent deficits. No risk factors for stroke after time of diagnosis were found to be significant.

The results of this study demonstrate that revascularization is associated with a significant reduction in stroke risk, both relative to prerevascularization rates and compared with medical management. According to these findings, surgical revascularization offers a safe and durable preventative therapy for stroke and should be pursued aggressively in this patient population 2).

Lo Presti et al. present the case of a 15-year-old boy with Sickle cell disease SCD-associated moyamoya disease harboring a intracranial pial arteriovenous fistula pAVF who developed a de novo venous aneurysm 8 months after undergoing indirect superficial temporal arterymiddle cerebral artery (MCA) bypass that was complicated by bilateral ischemia of the MCA territory. The pAVF was successfully treated with transarterial embolization using Onyx. The authors describe the possible pathophysiological mechanisms and management strategies for this rare occurrence 3).


Slingerland et al. described a challenging case where a patient with sickle cell disease undergoing standard of care management as prescribed by the Stroke Prevention Trial in Sickle Cell Anemia (STOP) and revascularization with pial synangiosis subsequently developed rapidly progressive disease in other cerebral vessels and suffered ischemic hemispheric stroke. This case demonstrates the success of management in accordance with American Heart Association (AHA) and American Stroke Association (ASA) guidelines, but also demonstrates critical areas where we lack understanding of disease progression 4).


1) , 2)

Newman S, McMahon JT, Boulter JH, Malcolm JG, Revuelta Barbero JM, Chern JJ, Barrow DL, Pradilla G. Revascularization Is Associated With a Reduced Stroke Risk in Patients With Sickle Cell-Associated Moyamoya Syndrome. Neurosurgery. 2022 Feb 10. doi: 10.1227/NEU.0000000000001847. Epub ahead of print. PMID: 35132969.
3)

Lo Presti A, Weil AG, Fallah A, Peterson EC, Niazi TN, Bhatia S. Treatment of a cerebral pial arteriovenous fistula in a patient with sickle cell disease-related moyamoya syndrome: case report. J Neurosurg Pediatr. 2015 May 22:1-5. [Epub ahead of print] PubMed PMID: 26053963.
4)

Slingerland AL, Karsten MB, Smith ER, Sobota AE, See AP. Two Sides of a Coin: Case Report of Unilateral Synangiosis and Contralateral Stroke Highlighting Consequences of Disease Progression and Efficacy of Revascularization in Sickle Cell Disease Associated Moyamoya Syndrome. Acta Haematol. 2021 Dec 8. doi: 10.1159/000521361. Epub ahead of print. PMID: 34879377.

Moyamoya disease classification

Moyamoya disease classification

The ischemic and hemorrhagic subtypes are difficult to diagnose prior to disease onset.

The intralateral and perilateral ventricular arteries on the original axial Time of flight magnetic resonance angiography images might suggest the hemorrhagic type of moyamoya disease prior to onset 1).

Unilateral and bilateral moyamoya disease (MMD).

Quasi Moyamoya disease

Asymptomatic Moyamoya Disease

Ischemic-type Moyamoya Disease

Suzuki and Kodoma classified the severity of moyamoya disease by progression of an occlusive process and the eventual appearance of collaterals based on serial cerebral angiographic evaluations and staged them, known as ‘Suzuki stages of Moyamoya disease’ which are mentioned under staging.

see Suzuki staging.


Traditional moyamoya disease (MMD) classification relies on morphological digital subtraction angiography (DSA) assessment, which do not reflect hemodynamic status, clinical symptoms, or surgical treatment outcome.

The Berlin MMD grading system is able to stratify preoperative hemispheric symptomatology. Furthermore, it correlated with postoperative new ischemic changes on MRI, and showed a strong trend in predicting clinical postoperative stroke. 2)


Ladner et al performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD).

Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow-weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0-5 points; Grade 2, 6-9 points; and Grade 3, 10 points.

In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI 1.1-22.6, p = 0.002). The area under the curve for individual PIRAMD factors was 0.67-0.72, and for the PIRAMD grade it was 0.845. There were 0/8 (0%), 10/18 (55.6%), and 18/20 (90%) symptomatic PIRAMD Grade 1, 2, and 3 hemispheres, respectively.

A scoring system for total impairment is proposed that uses noninvasive MRI parameters. This scoring system correlates with symptomatology and may provide a measure of hemodynamic severity in moyamoya, which could be used for guiding management decisions and evaluating intervention response 3).


In 2014 Hung et al. proposed a quantitative method using color-coded parametric quantitative DSA (QDSA) to improve prediction of the severity of MMD. The Td significantly correlated with conventional angiographic grading and with the status of hemodynamic impairment in patients with MMD. QDSA and Td measurements can provide a simple and quantitative angiographic grading system for patients with MMD. 4).


1)

Ishikawa M, Terao S, Kagami H, Inaba M, Naritaka H. Intralateral and Perilateral Ventricular Arteries on Original Axial Magnetic Resonance Angiography in Adult Moyamoya Disease. Eur Neurol. 2021 Mar 29:1-5. doi: 10.1159/000514429. Epub ahead of print. PMID: 33780954.
2)

Teo M, Furtado S, Kaneko OF, Azad TD, Madhugiri V, Do HM, Steinberg GK. Validation and Application for the Berlin Grading System of Moyamoya Disease in Adult Patients. Neurosurgery. 2020 Feb 1;86(2):203-212. doi: 10.1093/neuros/nyz025. PMID: 30864668.
3)

Ladner TR, Donahue MJ, Arteaga DF, Faraco CC, Roach BA, Davis LT, Jordan LC, Froehler MT, Strother MK. Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging. J Neurosurg. 2016 Mar 11:1-9. [Epub ahead of print] PubMed PMID: 26967789.
4)

Hung SC, Liang ML, Lin CF, Lin CJ, Guo WY, Chang FC, Wong TT, Chang CY. New grading of moyamoya disease using color-coded parametric quantitative digital subtraction angiography. J Chin Med Assoc. 2014 Aug;77(8):437-42. doi: 10.1016/j.jcma.2014.05.007. Epub 2014 Jul 12. PMID: 25028291.

Moyamoya Disease Epidemiology outside of Asia

Moyamoya Disease Epidemiology outside of Asia

In a Nationwide Inpatient Sample (NIS), patients presenting with ischemic stroke were more likely to be 65 years and older (p < 0.001); patients presenting with intracranial hemorrhage (ICH) were more likely to be 65 years and older (p < 0.001), male (p = 0.027), and Asian (p = 0.007); those presenting with seizure were more likely to be less than 10 years old (p = 0.002) and African American (p < 0.001); and those presenting with headache were more likely to be between 10 and 19 years old (p = 0.008).

The findings demonstrate that the distinct presentations of Moyamoya are associated with patient age, gender, and race. This is the largest study of its kind and adds to the collective understanding of this rare but life-threatening condition 1).


Studies from outside of Asia are rare. In Washington state and California, the incidence of MMD was reported to be 0.086/100,000 based on 298 patients. The incidence was the highest in Asians, followed by Blacks, Whites, and Hispanics. The incidence in Asian Americans was 4.6 times higher than that in Whites. Female preponderance was also noted 2).

African-Americans had an earlier disease onset with a median age of 18. However, a more recent study based on the Nationwide Inpatient Sample database reported that MMD appears to be distributed among the races according to their relative proportions in the USA population 3).

From 2005 to 2008, there were an estimated 7,473 (2,236 pediatric and 5,237 adult) patients admitted with a diagnosis of MMD in the USA. MMD patients were most frequently Caucasians. Overall, ischemic stroke was the most common reason for admission in both children and adults. Hemorrhagic stroke was more frequent in adults compared with children, and there was a bimodal age distribution with peaks in the first and fourth decades of life. Female-to-male ratio was 2.2. Thus, MMD in the USA does not seem to differ from East Asian MMD.


The incidence of Moyamoya disease (MMD) in Europe is not well known. In those affected, the risk of brain hemorrhage is considered low. A study of Birkeland et al. aimed to investigate the incidence and clinical presentation of MMD in the Danish population.

Eligible patients were identified in the Danish National Patient Register from 1994 to 2017. They collected clinical and radiological data from individual patient records from neurological, neurosurgical, and pediatric units across Denmark. The diagnosis was validated according to established criteria. They also extracted basic demographic data on the cohort from the Danish Civil Registration System.

A total of 52 patients fulfilled the diagnostic criteria for MMD. Most cases were native Danes and only 15% of cases had an East Asian background. The ratio of female to male patients was 1.8, and the incidence had two peaks: one in childhood and another in young middle age. Until 2007, MMD was only diagnosed sporadically. From 2008 onwards, the incidence rate was 0.07 per 100 000 person-years (95% confidence interval 0.05-0.09 per 100 000 person-years). The most common mode of presentation was ischemic stroke (33%), followed by hemorrhage (23%), headache (17%), and transient ischemic attack (14%).

MMD is rare in Denmark, but associated with a considerable risk of hemorrhage. Thus, MMD should be considered in the workup for ischemic as well as hemorrhagic stroke in children and middle-aged Caucasian4).


1)

Fuentes AM, Chiu RG, Mehta AI. Disparities in the symptomatic presentation of Moyamoya disease in the United States: A nationwide all-payer analysis. J Clin Neurosci. 2021 May;87:92-96. doi: 10.1016/j.jocn.2021.02.019. Epub 2021 Mar 20. PMID: 33863543.
2)

Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology. 2005;65(6):956-958. doi:10.1212/01.wnl.0000176066.33797.82
3)

Kainth D, Chaudhry SA, Kainth H, Suri FK, Qureshi AI. Epidemiological and clinical features of moyamoya disease in the USA. Neuroepidemiology. 2013;40(4):282-287. doi:10.1159/000345957
4)

Birkeland P, Tharmabalan V, Lauritsen J, Ganesan V, Bjarkam CR, von Weitzel-Mudersbach P. Moyamoya disease in a european setting: A danish population-based study [published online ahead of print, 2020 Jul 15]. Eur J Neurol. 2020;10.1111/ene.14439. doi:10.1111/ene.14439

Book: Moyamoya Disease Explored Through RNF213: Genetics, Molecular Pathology, and Clinical Sciences

Moyamoya Disease Explored Through RNF213: Genetics, Molecular Pathology, and Clinical Sciences (Current Topics in Environmental Health and Preventive Medicine)

Moyamoya Disease Explored Through RNF213: Genetics, Molecular Pathology, and Clinical Sciences (Current Topics in Environmental Health and Preventive Medicine)

List Price: $159.00
This book presents the latest findings on biological, epidemiological, and clinical investigations of RNF213, which is thought to be involved in many biological processes and plays a key role in cerebro- and cardiovascular disease . By discussing the epidemiology and genetic epidemiology of the disease with a particular focus on the molecular function of RNF213, research using animal models, diagnosis, therapy and clinical management around the world, this work makes a valuable contribution to the study of the disease.
Moyamoya Disease Explored Through RNF213 is an indispensable resource for both beginning and experienced researchers, pediatricians, neurologists, and neurosurgeons who are seeking comprehensive information on adult and childhood stroke.

Product Details

  • Published on: 2017-03-22
  • Original language: English
  • Number of items: 1
  • Dimensions: 9.30″ h x .0″ w x 6.10″ l,
  • Binding: Hardcover
  • 185 pages

Akio Koizumi, Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University

Kazuhiro Nagata, Laboratory of Molecular and Cellular biology, Faculty of Life Sciences, Kyoto Sangyo University
Kiyohiro Houkin, Department of Neurosurgery, Graduate School of Medicine, Hokkaido University

Teiji Tominaga, Department of Neurosurgery, Tohoku University School of Medicine
Susumu Miyamoto, Department of Neurosurgery, Graduate School of Medicine, Kyoto University
Shigeo Kure, Department of Pediatrics, Tohoku University School of Medicine
Elizabeth Tournier‐Lasserve, CHU Paris‐GH St‐Louis Lariboisière F‐Widal ‐ Hôpital Lariboisière

Today: 4th International Moyamoya Meeting

4th International Moyamoya Meeting

JULY 2-4, 2015
Berlin, Germany
http://www.moyamoya2015.com/

Thursday, July 2, 2015, 11:45 – 18:15 hrs
“How-I-do-it”-Workshop

TH.01 Surgical Techniques in Moyamoya Vasculopathy – Tricks of the Trade
Chair Peter Vajkoczy (Berlin)

11:45 TH.01.01 Introduction
Peter Vajkoczy (Berlin), S. Konnry
Part I
12:00 TH.01.02 General Principles of direct BypassSurgery
Marcus Czabanka (Berlin/D)
12:15 TH.01.03 General Principles of indirect BypassSurgery
Satoshi Kuroda (Toyama/J)
Part II – Indirect Revascularization
12:30 TH.01.04 Multiple burr holes
Thomas Blauwblomme (Paris/F)
12:45 TH.01.05 Encephalomyosynangiosis (EMS)
Peter Vajkoczy (Berlin/D)
13:00 TH.01.06 Encephaloduroarteriosynangiosis (EDAS) – pediatric
Edward Smith (Boston/USA)
13:15 TH.01.07 Encephaloduroarteriosynangiosis (EDAS) – adult
Nestor Gonzalez (Los Angeles/USA)
13:30 TH.01.08 Encephaloduroarteriomyosynangiosis (EDAMS)
N. N.
13:45 TH.01.09 Bifrontal Encephaloduroperiostalsynangiosis
Luca Regli (Zurich/CH)
Part III – Direct Revascularization
14:00 TH.01.10 STA-MCA bypass
Peter Vajkoczy (Berlin)
14:15 TH.01.11 Double barrel STA-MCA bypass
Robert F. Spetzler, John E. Wanebo (Phoenix/USA)
14:30 TH.01.12 Occipital artery posterior cerebral and middle cerebral artery bypass
Ken Kazumata (Sapporo/J)
14:45 – 15:30 Coffee Break
15:30 TH.01.14 Superficial temporal artery-anterior cerebral artery /middle cerebral artery double bypasses with long graft for Moyamoya disease – surgical technique and angiographical evaluation
Akitsugu Kawashima, Takakazu Kawamata, Koji Yamaguchi, Yoshikazu Okada (Chiba/J, Tokyo/J)
15:45 TH.01.15 Double anastomosis using only one branch of STA
Fady T. Charbel (Chicago/USA)
Part IV – Combined Revascularization
16:00 TH.01.16 STA-MCA bypass + EMS
Peter Vajkoczy (Berlin)
16:15 TH.01.17 STA-MCA bypass + EMS/EDMS
Kiyohiro Houkin (Sapporo/J)
16:30 TH.01.18 STA-MCA bypass + pansynangiosis
Satoshi Kuroda (Toyama/J)
16:45 TH.01.19 STA-MCA bypass + Encephaloduroperiostalsynangiosis
Sepideh Amin-Hanjani (Chicago/USA)
Part V – Rescue Strategies for Repeat Surgery
17:00 TH.01.20 Omentum transposition
Gary K. Steinberg (Stanford/USA)
17:15 TH.01.21 ECA-MCA bypass with radial artery graft
Satoshi Hori (Berlin)
17:30 TH.01.22 OA-MCA / OA-PCA bypass
Gary K. Steinberg (Stanford/USA)
17:45 TH.01.23 Auricular artery / MCA bypass
Luca Regli (Zurich/CH)

 

Update: Asymptomatic Moyamoya Disease

Asymptomatic Moyamoya Disease

J.Sales-Llopis
Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain
In asymptomatic Moyamoya Disease, the patient should previously have no ischemic or hemorrhagic episode and be neurologically free.
They who had previously experienced any episode suggestive of TIA, cerebral infarction, intracranial hemorrhage, seizure, or involuntary movement caused by moyamoya disease should be excluded. Careful medical interview should be performed to distinguish moyamoya disease-related headache from non-specific headache such as tension-type headache 1).

Epidemiology

The prevalence and incidence of asymptomatic moyamoya disease are still unclear. Previously, asymptomatic patients with moyamoya disease have rarely been sporadically reported. Screening of family members with moyamoya disease has also identified small number of asymptomatic patients. Therefore, the incidence of asymptomatic moyamoya disease had been believed very low. In fact, Yamada et al. (2005) reported the results of a nation-wide questionnaire conducted in 1994 and identified 33 asymptomatic patients (1.5%) out of a total of 2,193 patients 2).

Diagnosis

Recent development of a non-invasive magnetic resonance examination has increased the opportunity to identify asymptomatic patients with moyamoya disease who have experienced no cerebrovascular events. However, their clinical features, prognosis, and treatment strategy are still unclear because of small number of subjects and short follow-up periods.

Survey

The first multi-center, nation-wide survey focused on asymptomatic patients with moyamoya disease was conducted between 2003 and 2006 in Japan. as a result, totally 40 patients were enrolled from 12 hospitals. Their mean age was 41.4 years ranging from 13 years to 67 years. The female-to-male ratio was 2.1. Clues to the diagnosis were tension-type headache in 14 patients, dizziness in 5, and head trauma in 4. Five patients were incidentally diag- nosed on MrI and Mra performed for a brain health check-up. Five diagnoses were made on MrI and Mra performed for screening, because a member of their family had moyamoya disease diagnosed. They were siblings in two and offspring in three. The remaining seven cases were diagnosed on MrI and Mra performed because of an unrelated disease in other organs. Therefore, the prevalence and incidence may be much higher than considered before. The female-to-male ratio and mean age of the patients in these studies were very similar to those of moyamoya disease as a whole 3).

Registry

Therefore, Kuroda et al. have designed the Asymptomatic Moyamoya Registry (AMORE) study in Japan. The objectives of this nation-wide, multi-center prospective study are to clarify long-term prognosis of asymptomatic patients with moyamoya disease and to determine the risk factors that cause ischemic and hemorrhagic stroke in them 4).

Treatment

Asymptomatic moyamoya disease is not a “silent” disorder and readily progress to cause ischemic and hemorrhagic stroke. It would also be essential to repeat MRI and MRA at regular intervals when asymptomatic patients are conservatively followed up to detect disease progression before any cerebrovascular events occur 5).
1) , 3) Kuroda S, Hashimoto N, Yoshimoto T, Iwasaki Y; research Committee on Moyamoya disease in Japan: radiological findings, clinical course, and outcome in asymptomatic moyamoya disease: results of multicenter survey in Japan. Stroke 38: 1430–1435, 2007
2) Yamada M, Fujii K, Fukui M: [Clinical features and outcomes in patients with asymptomatic moyamoya disease—from the results of nation-wide question- naire survey]. No Shinkei Geka 33: 337–342, 2005
4) , 5) Kuroda S; AMORE Study Group. Asymptomatic Moyamoya Disease: Literature Review and Ongoing AMORE Study. Neurol Med Chir (Tokyo). 2015 Mar 15;55(3):194-8. doi:10.2176/nmc.ra.2014-0305. Epub 2015 Feb 20. PubMed PMID: 25739434.