Progressive Steno-occlusive Disease Research Articles

Moyamoya Disease Masquerading as Hemiplegic Migraine in a Child: A Case Report From India

Moyamoya disease (MMD) is a chronic progressive steno-occlusive disease of the intracranial arterial vessels and their branches characterized by puff smoke appearance on angiography. Multifocal neurological insults and deficits are commonly observed in children with MMD. A 7-year-old boy presented with multiple episodes of transient hemiparesis preceded by headache, vomiting, and visual auras was initially labeled as sporadic hemiplegic migraine according to the International Headache Society criteria. However, the rare association of hemiplegic migraine with MMD compelled us to perform magnetic resonance imaging and digital subtraction angiography, which revealed MMD as the underlying cause for the alternating hemiplegia and headaches in the child.

Abstract WP247: Potential Predictors for Progression of Adult Moyamoya Disease: A Study From Multicenter Registry

Background and aims: Moyamoya disease refers to a chronic progressive steno-occlusive disease at the distal portion of the internal carotid arteries (ICAs) and compensatory abnormal collateral vessel formation. However, the incidence of progression and its’ related factors in adult moyamoya disease has not been well known. Our study was to investigate the prevalence of progression of steno-occlusion of intracranial vessels and clinical outcome in the patients with adult moyamoya disease. Methods: From Jan 2001 to Jun 2021, we included the patients who was diagnosed with symptomatic or asymptomatic moyamoya disease from moyamoya registries of 4 hospitals in Korea. We excluded patients who did not have any follow-up angiography more than 1 year after baseline angiography [digital subtraction angiography (DSA) or magnetic resonance angiography (MRA)]. We adopted Suzuki’s angiographic staging and MRA score for the analysis. Results: A total of 293 moyamoya patients were included, and mean follow-up period was 92.7 ±52.8 months. Among them, progression of vessel stenosis in DSA and/or MRA was found in 110 patients (37.5%). Recurrent stroke occurred in 39/183 (21.3%) in non-progression group and 40/110 (36.4%) in progression group. Clinical characteristics were not significantly different between two groups. However, previous ischemic stroke history is independently associated with angiographic progression (odds ratio, 3.384 [95% CI, 1.521-7.531]) in multivariable logistic regression analysis. Conclusions: Occlusive arterial status worsened in one-third of the patients with adult moyamoya disease during approximately 8 years of follow-up. Careful neurological and radiological follow-up would be essential to prevent additional stroke occurrence, especially in patients with a history of cerebral infarction.

Abstract TMP63: Structural Network Changes In Children With Moyamoya Disease Prior To Surgical Intervention

Purpose: Moyamoya disease/syndrome (MMD) is a progressive steno-occlusive disease involving the intracranial arterial circulation. Long term stenosis/hypoperfusion can lead to intellectual disability and cognitive impairment even in the absence of documented infarct. We aim investigate any underlying network abnormalities in MMD patients with no apparent ischemic injury. Materials and Methods: We retrospectively reviewed children with MMD with normal appearing parenchyma on conventional MRI. Control patients were selected from our existing database. Clinical, surgical and demographic data, including degree of stenosis as measured semi-quantitatively on MRA, were collected. Patients with documented infarcts, low quality DTI, and NF1 were excluded from the analysis. Group and correlational connectometry with degree of stenosis were performed. Results: A total of 28 patients were reviewed with 16 patients included in the study. Median (and interquartile range) age was 10.5 (8.5 - 13.5). Between group connectometry analysis identified infratentorial and supratentorial decreased connectivity in patients compared to controls, specifically in: middle cerebellar peduncle, corpus callosum, right parietopontine tract, superior cerebellar peduncle, left inferior fronto-occipital fasciculus. (Figure 1) In addition, we found negative correlation between the degree of stenosis and structural connectivity of multiple white matter pathways. Conclusion: Our findings reveal abnormal structural connectivity in children with MMD in the absence of infarcts on conventional MRI. Connectomics offers a unique opportunity to study the effect of long-term stenosis/hypoperfusion on cerebellar-cerebral networks and provide new insights into the mechanism of the structural plasticity/reorganization in these patients before bypass surgery. Future research is needed to determine longitudinal network changes before and after surgery.

Abstract 15484: Combined Coronary and Carotid Artery Involvement in a Caucasian Patient With Moyamoya Disease

Introduction: Moyamoya disease (MMD) is a rare, progressive steno-occlusive disease of the intracranial carotid arteries. This is primarily a cerebrovascular disease and is mostly seen in young Japanese patients. We report a case of severe stenosis in the distal left circumflex artery (dLCx) in a non-Japanese patient with previously diagnosed MMD. Case presentation: A 33-year-old Caucasian female with history of MMD and 2 CVAs presented with chest pain for 2 days. Her only medication at home was aspirin. There was no history of hypertension, diabetes mellitus, or tobacco use. There was no family history of early CAD. Physical examination was positive for tachycardia but negative for carotid or femoral bruits. Neurologic examination revealed decreased touch sensation and diminished deep tendon reflexes on the left side. ECG demonstrated tachycardia with T wave inversions in leads III and ST depression in lead II. Acute CVA was ruled out with an MRI. Cardiac troponins were minimally elevated with peak of 0.12 ng/dl. An initial diagnosis of NSTEMI was made; patient was loaded with aspirin, clopidogrel and started on a heparin drip. Cardiac catheterization on the following day revealed single vessel CAD in the dLCx, with 80% stenosis and TIMI flow 2. A drug eluting stent was successfully placed in the dLCx. Angiogram post-stent placement showed optimal angiographic result with TIMI 3 flow. The patient was discharged home on dual antiplatelet therapy, statin, beta-blocker and ACE inhibitor. Discussion: MMD is thought to affect the coronary arteries from fibrous intimal thickening and histopathology of these coronary lesions show a homogenous, soft intimal proliferation with minimum lipid deposition and without substantial inflammatory cell infiltration. Although the combined involvement of carotid and coronary artery stenosis is rare, coronary involvement should be considered as one of the causes of ischemic heart disease in young patients with MMD. To the best of our knowledge, this is the first reported case of combined involvement of carotid and coronary artery stenosis in a Caucasian patient with previously diagnosed MMD. It is imperative to educate patients with MMD about possible CAD so that they seek immediate medical attention if cardiac symptoms occur.

Moyamoya disease in a 29-year-old female of Indian Origin

The case presented here is a 29-year-old female patient with complaints of weakness over the left upper and lower limbs for 2 weeks. Digital subtraction angiography of the brain was suggestive of cerebral arteries, showing proliferation of cortical as well as collateral arteries arising from the internal carotid arteries (ICAs). Moyamoya is a progressive steno-occlusive disease at the terminal portions of the bilateral ICAs, with the development of “moyamoya vessels” giving a “Puff of Smoke” appearance on catheter angiography. Cerebral angiography is gold standard for diagnosis and helpful for detecting aneurysm and for surgical planning. There is no standardized surgical strategy for the treatment of this disease. Innumerable revascularization procedures have been employed with the aim of decelerating the progression of disease. Recognition of various symptoms of moyamoya would enable early diagnosis so that it could be treated surgically, as soon as possible, leading to a better neurological outcome.

Diagnosis and treatment of adult Moyamoya disease

Moyamoya disease (MMD) refers to a chronic progressive steno-occlusive disease at the distal portion of the internal carotid artery with abnormal collateral vessel formation of unknown etiology. The definite diagnosis of MMD requires cerebral angiography or magnetic resonance angiography and/or magnetic resonance imaging after excluding other underlying diseases, particularly in adult patients. The treatment aims to improve regional cerebral blood flow to prevent cerebral ischemic events and alleviate hemodynamic instability that can provoke cerebral hemorrhage. Although various surgical revascularization methods have been introduced, combined revascularization surgery including direct revascularization is preferred over indirect revascularization only in adult MMD patients. Several recent studies have shown that surgical treatment has better outcomes and prognosis for symptomatic hemodynamically unstable MMD patients with both ischemic and hemorrhagic presentations. For asymptomatic patients, follow up with appropriate imaging is recommended. Surgery should be considered when new symptoms emerge with hemodynamic aggravation.

Rescue Cerebral Revascularization in Patients with Progressive Steno-Occlusive Ischemia of the Anterior Intracranial Circulation

Despite the failure of 2 randomized controlled trials assessing the utility of bypass for steno-occlusive cerebrovascular disease, a specific subset of patients with progressive and/or refractory symptoms may benefit from cerebral revascularization. This study assessed the efficacy and outcomes of bypass surgery for progressive and/or refractory steno-occlusive cerebrovascular disease. A retrospective database review was performed to identify patients who underwent bypass for progressive and/or refractory steno-occlusive disease of the internal carotid artery or middle cerebral artery over a 4-year period (July 2014-July 2018). Surgical and clinical outcomes were recorded. Seventeen patients (average age 62 ± 11 years) underwent extracranial-intracranial bypass for refractory and/or progressive steno-occlusive disease of the internal carotid artery or middle cerebral artery. Thirteen patients presented with stroke, 3 presented with recurrent transient ischemic attacks, and 1 presented with progressive hemiparesis. All patients had preoperative perfusion imaging deficits. Average temporary clip time was 35 ± 8 minutes. An interposition graft was used in 7 patients. There was 3 ischemic and 3 hemorrhagic perioperative strokes (35%); all were minor or related to anticoagulation. Over an average of 10 ± 10 months of follow-up, there were no ischemic strokes in the bypass-dependent territories. Of 17 patients, 16 (78%) achieved a Glasgow Outcome Scale score ≥4, and 13 (85%) achieved a modified Rankin Scale score ≤2. Bypass for steno-occlusive disease of the anterior intracranial circulation is a potentially effective treatment for patients with progressive and/or refractory ischemic symptoms, although the complication rate is significant. Optimal patient selection criteria and timing of surgery remain open questions.

Moyamoya syndrome and PHACE syndrome: clinical and radiographic characterization of the intracranial arteriopathy and response to surgical revascularization.

PHACE syndrome (PHACES) has been linked to cervical and cerebral vascular anomalies, including persistent embryonic anastomoses and progressive steno-occlusive disease. However, no prior studies have documented the long-term response of PHACES patients with moyamoya disease to surgical revascularization with pial or myosynangiosis. The authors present their experience with 8 consecutive patients with PHACES and moyamoya disease. Retrospective review of patients who underwent pial synangiosis revascularization for moyamoya disease with concurrent diagnosis of PHACES. A total of 8 patients out of 456 surgically treated moyamoya patients had a diagnosis of PHACES. All patients were female, and their average age at the time of surgical treatment was 9.3 years (range 1.8-25.8 years). Five patients had associated basilar artery anomalies or stenosis. All patients had symptomatic narrowing of the petrous segment of the internal carotid artery with tortuous collateralization. Three patients underwent unilateral pial or myo-synangiosis and 5 underwent bilateral procedures. The average hospital length of stay was 5.0 days (range 3-7 days). There were no postoperative complications. Follow-up ranged from 8 to 160 months (average 56 months). Seven of 8 patients have had follow-up angiograms and all had Matsushima grade A or B collateralization without progression of stenosis in other locations. All patients had reduced cortical FLAIR signal on 6-month follow-up MRI and no evidence of new radiographic or clinical strokes. Patients with moyamoya disease and PHACES had an intracranial arteriopathy characterized by ectactic anterior vasculature with concomitant basilar artery stenosis, and were all female. The patients had both radiographic and clinical responses to pial synangiosis. The surgical treatment of these patients can be challenging given facial hemangiomas located near the surgical field. Patients with unilateral disease did not have evidence of progression in other cerebral circulation during the given follow-up period.

Adult moyamoya angiopathy in Bourgogne-Franche-Comté: Epidemiology, diagnosis and management

IntroductionMoyamoya angiopathy (MMA) is a progressive steno-occlusive disease of the distal internal carotid arteries mainly described in Asia. It induces the development of collateral vascular networks to reduce chronic cerebral hypoperfusion. Symptoms depend on the patient's age in Asia: children are at greater risk of transient or constituted ischemic events, whereas adults are more exposed to hemorrhagic stroke. Data from the literature seem to show that the pattern of MMA in western countries differs from that in Asia. Material and methodsA retrospective study of patients with MMA was conducted in Bourgogne-Franche-Comté (mid-eastern France). Clinical data (symptoms, risk factors, age at diagnosis, number and timing of recurrences, type of treatment) as well as radiological data (angiographic findings, Suzuki's grade) were analyzed. ResultsSeventeen adult patients (9 men, 53%) were followed at the university hospitals of Besançon and Dijon from 2009 to 2016. Fourteen patients (83%) had bilateral disease. The mean age at diagnosis was 49 years (±16), 83% of the patients were Caucasian and 17% originated from Maghreb. Only 17% of the hemispheres had a hemorrhagic form. Ischemic form was more frequent before diagnosis with transient ischemic attack (24% of patients) and stroke (83% of patients). With medical treatment, 9 patients suffered from stroke recurrence (53% of patients) with an average delay of 22.7±34 months. Three patients (18%) had combined surgical management by encephelo-synangiosis and superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis, without symptom recurrence after treatment with an average follow up of 14 months. ConclusionMMA remains a rare cerebrovascular disease in Europe and requires multidisciplinary care. Epidemiological analysis showed differences with the Asian population, especially the predominance of ischemic forms in adults.

Moyamoya Syndrome with contra lateral DACA aneurysm: First Case report with review of literature

Abstract Moyamoya disease is a progressive steno-occlusive disease of bilateral internal carotid artery with the development of fine collateral vessels and is an angiographic diagnosis. Concurrent Moyamoya disease with intracranial aneurysm had been reported in literature by various authors. Moyamoya disease is reported with aneurysm at various locations including basilar tip, anterior choroidal artery, posterior choroidal artery, anterior cerebral artery and middle cerebral artery. After reviewing literature thoroughly there is not a single case report on Moyamoya disease with isolated distal anterior cerebral artery aneurysm with the best of our knowledge. Here we are reporting a case of Moyamoya disease of left petrous and cavernous part of internal carotid artery with contralateral distal anterior cerebral artery aneurysm in a 36-year-old male.

Moya Moya Disease in a 5 Year Child-presenting as Hemiparesis withMedullary Sponge Kidneys

Moya moya disease is a very rare cause of acute stroke in pediatrics age group. The disease was first described by Takeuchi and Shmuziin 1957.since the disease is common in japan and cases have been reported mostly in japan but cases have been reported rarely from non-Japanese regions including India. Moya moya disease is a progressive steno occlusive disease at terminal portion of internal carotid arteried with development of collateral channels of circulation. We report a case of 5 years male child who presented with history of fall 1 day back followed by sudden loss of speech and weakness of right side of the body. Patient was diagnosed moya moya disease on basis of MRI angiography.

Cellular Functions and Gene and Protein Expression Profiles in Endothelial Cells Derived from Moyamoya Disease-Specific iPS Cells.

Background and purposeMoyamoya disease (MMD) is a slow, progressive steno-occlusive disease, arising in the terminal portions of the cerebral internal carotid artery. However, the functions and characteristics of the endothelial cells (ECs) in MMD are unknown. We analyzed these features using induced pluripotent stem cell (iPSC)-derived ECs.MethodsiPSC lines were established from the peripheral blood of three patients with MMD carrying the variant RNF213 R4810K, and three healthy persons used as controls. After the endothelial differentiation of iPSCs, CD31+CD144+ cells were purified as ECs using a cell sorter. We analyzed their proliferation, angiogenesis, and responses to some angiogenic factors, namely VEGF, bFGF, TGF-β, and BMP4. The ECs were also analyzed using DNA microarray and proteomics to perform comprehensive gene and protein expression analysis.ResultsAngiogenesis was significantly impaired in MMD regardless of the presence of any angiogenic factor. On the contrary, endothelial proliferation was not significant between control- and MMD-derived cells. Regarding DNA microarray, pathway analysis illustrated that extracellular matrix (ECM) receptor-related genes, including integrin β3, were significantly downregulated in MMD. Proteomic analysis revealed that cytoskeleton-related proteins were downregulated and splicing regulation-related proteins were upregulated in MMD.ConclusionsDownregulation of ECM receptor-related genes may be associated with impaired angiogenic activity in ECs derived from iPSCs from patients with MMD. Upregulation of splicing regulation-related proteins implied differences in splicing patterns between control and MMD ECs.

Histopathological Characteristics of Distal Middle Cerebral Artery in Adult and Pediatric Patients with Moyamoya Disease

Moyamoya disease (MMD) is a unique progressive steno-occlusive disease of the distal ends of bilateral internal arteries and their proximal branches. The difference in clinical symptoms between adult and children MMD patients has been well recognized. In this study, we sought to investigate the phenomenon through histopathological study. Fifty-one patients underwent surgical procedures for treatment of standard indications of MMD at Kyoto University Hospital. Fifty-nine specimens of MCA were obtained from MMD patients during the surgical procedures. Five MCA samples were also obtained in the same way from control patients. The samples were analyzed by histopathological methods. In this study, MCA specimens from MMD patients had significantly thinner media and thicker intima than control specimens. In subsequent analysis, adult (≥ 20 years) patients had thicker intima of MCA compared to pediatric (< 20 years) patients. There is no difference in internal elastic lamina pathology between adult and pediatric patients. Our results indicated that the pathological feature of MMD in tunica media occurs in both adult and pediatric patients. However, the MMD feature in tunica intima of MCA is more prominent in adult patients. Further analysis from MCA specimens and other researches are necessary to elucidate the pathophysiology of MMD.

Review of past and present research on experimental models of moyamoya disease

Moyamoya disease (MMD) is characterized by a progressive steno-occlusive disease affecting the terminal portions of the cerebral internal carotid artery (ICA) and by formation of an abnormal vascular network at the base of the brain. Several pathogeneses, including inflammation, immune complex, upregulation of angiogenic factors, and abnormality of endothelial progenitor cells (EPCs) have been hypothesized. However, the mechanisms of MMD are largely unknown, and in vivo and in vitro models of MMD have not yet been established. Previously, inflammation- and immune-complex-related animal models have been reported but failed to reproduce severe stenotic lesions in the terminal portion of ICA. Thereafter, several clinical studies revealed that angiogenic activity of circulating EPCs was defective in MMD patients. These results suggested that the function and quantity of EPCs could be useful as a cellular model of MMD. Very recently, RING finger protein 213 (RNF213) was identified as an MMD susceptibility gene, a discovery that led to the efforts to generate gene mutation-based animal models. Although RNF213 knockout animal models have not yet successfully represented the phenotype of MMD, they have provided new insights into the role of RNF213 in remodeling after vascular injury and postischemic angiogenesis. Furthermore, the use of induced pluripotent stem cells (iPSCs) and an appropriate differentiation protocol have made it possible to obtain abundant quantities of MMD-specific vascular cells. In summary, studies have shown that endothelial cells derived from MMD-iPSCs have impaired angiogenic activity, which is a finding consistent with the results of EPC studies. Further studies are needed to create true MMD-specific experimental models to promote understanding of MMC pathogenesis and aid drug development.

E-014 Changes in Posterior Circulation Arterial Flows after Revascularization Surgery in Moyamoya Disease: A Quantitative MRI Study

Background and purposeMoyamoya disease and syndrome are well known to affect the anterior cerebral circulation by progressive steno-occlusive disease of the supraclinoid internal carotid arteries. Less attention has been paid...

An update on the diagnosis and treatment of adult Moyamoya disease taking into consideration controversial issues

Moyamoya disease (MMD) is characterized by a chronic progressive steno-occlusive disease at the distal portion of the internal carotid artery (ICA) with abnormal Moyamoya vessel (MMV) development without associated diseases. Recent advances in radiologic tests have increased the number of MMD patients. Beyond detection improvement by magnetic resonance angiography (MRA) or cerebral angiography, predicting factors for disease severity, future hemorrhage, clinical outcome, post-op complications, and technical advances in assessing cerebral hemodynamics have been increasingly reported. Although treatment of pediatric MMD is well established, controversy remains over the treatment in adult patients. In particular, there are debates over the disease entity of adult MMD, contralateral progression in adult unilateral MMD, treatment strategy for asymptomatic adult MMD, and the association of MMD with thyroid disease. The purpose of this review is to provide an update on the diagnosis and treatment of adult MMD while addressing controversial issues.

Abstract TMP40: Revascularization in Patients with Moyamoya Decreases Abnormally High Posterior Circulation Arterial Flows Measured by Quantitative Magnetic Resonance Angiography

Introduction: Moyamoya disease and syndrome are well known to affect the anterior cerebral circulation by progressive steno-occlusive disease of the supraclinoid internal carotid arteries. Less attention has been paid to changes in posterior arterial circulation hemodynamics in this condition. We sought to better understand the latter by using a relatively novel non-invasive imaging technique: quantitative magnetic resonance angiography (qMRA). Hypothesis: We assessed the utility of qMRA to detect changes in arterial posterior arterial circulation flows before and after surgical revascularization. Methods: Retrospective review of patients who met the following inclusion criteria: (1) diagnosis of moyamoya disease or syndrome with revascularization surgery at the Stanford University between September 2008 and March 2012; (2) preoperative and postoperative qMRA scans on record within a two-year time frame; and (3) high-quality qMRA images without motion artifact. Cerebral blood-vessel flow was quantified after non-contrast magnetic resonance imaging through the use of a commercially available software tool: non-invasive optimal vessel analysis (NOVA, VasSol, Chicago, USA). Results: A total of 191 patients underwent 281 surgeries in this period of time. Of these, a cohort of 64 patients (78% female, mean age 38.5 years, 55% unilateral disease) had preoperative and postoperative qMRA studies. Preoperative arterial flows in the posterior circulation were markedly elevated compared to normative data. These flows significantly decreased after revascularization (94% direct STA-MCA bypass): right posterior cerebral artery 145 ml/min pre-surgery, 123 ml/min post-surgery, p=0.005; basilar artery 264 ml/min pre-surgery, 222ml/min post-surgery, p=0.0038. Conclusion: Quantitative MRA shows that posterior circulation arterial flows are markedly increased in patients with moyamoya. After revascularization, there is an overall decrease in these flows that is significant in the basilar artery and right posterior cerebral artery. Further use of qMRA might be warranted to better understand moyamoya hemodynamics before and after surgery.

Adult onset moyamoya disease: Institutional experience

Moyamoya disease is a progressive steno-occlusive disease of bilateral carotid forks with the formation of fine collateral vascular network and is an angiographic diagnosis. We analyzed case records of 11 patients with "adult-onset moyamoya disease." Six patients presented with intracranial hemorrhage (intracerebral and/or intraventricular) and 5 with focal ischemia. Angiography revealed bilateral Internal carotid artery involvement in 8 patients and unilateral involvement in 3. Posterior cerebral artery involvement was seen in 3 patients. Saccular aneurysm involving posterior circulation was seen in only 1 patient. Although rare, adult-onset moyamoya disease should be considered as one of the causes for intracerebral and intraventricular hemorrhage in adults.

Analysis of class II genes of human leukocyte antigen in patients with Moyamoya disease

Moyamoya disease is a progressive stenoocclusive disease at the terminal portion of the bilateral internal carotid arteries. An unusual vascular network is formed as a result of ishemic change of cerebrovascular system. Although some investigations suggested possible etiological factors of Moyamoya disease, the etiology is still unknown. To elucidate the genetic factors of Moyamoya disease, class II genes of human leukocyte antigen (HLA) were analyzed at the DNA level. The DNA typing of HLA was performed in the unrelated Japanese patients with definite Moyamoya disease using extracted genomic DNA from the leukocyte. The genotype was confirmed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) technique. The class II genotypes were analyzed in 71 samples. As a result, several alleles of classII genes showed significant association with Moyamoya disease. DQB1*0502 had positive association with the disease. On the other hand DRB1*0405 and DQB1*0401 had negative association. Moyamoya disease seems to have a genetic background in its etiology because certain alleles of HLA are associated with Moyamoya disease.