INTRODUCTION:

MOYAMOYA is a Japanese term that translates to "a fuzzy thing like puffs of cigarette smoke floating in the air". In the 1960s, Takaku, Suzuki, and others described moyamoya disease in Japan^1,5. Moyamoya disease is a rare vascular (blood vessel) disease in which blood flow to the brain is restricted due to blockage or narrowing of the carotid artery in the skull. Small blood vessels then form at the base of the skull to continue supplying oxygen to the skull^5,9. The development of discernible collateral vessels seen on imaging, particularly cerebral angiography is caused by chronic progressive arterial occlusion in Willis' ring. It can appear in both children and adults, but the clinical characteristics are different^3,10. The pathogenesis of intriguing moyamoya disease is not well understood. Brain hemorrhage occurs in a small number of people (mostly adults) who have cerebral ischemia. Recently, large-scale studies on the detection and treatment of MMD are being conducted in China, Japan, and Korea. These articles cover aspects such as diagnosis, clinical symptoms, epidemiology, genetics, radiological evaluation, pathology, and treatment options for MMD^2,5. The cause of my illness is unknown. Narrowing of blood vessels in the brain can result from trauma or genetic abnormalities. There may be a link between the disease and neurofibromatosis, or a procedure such as an x-ray of the skull or heart surgery, or a treatment such as chemotherapy. She was seen by a physical therapist, occupational therapist, and speech therapist, and was discharged home without further treatment indications².

Figure 1. Growth of moyamoya disease.

The National Institutes of Health Stroke Scale (NIHSS), a systematic assessment tool that provides a quantitative measure of stroke-related neurological deficits, was found to be zero⁹. Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized by progressive narrowing of the intracranial portions of the distal internal carotid artery (ICA) and the primary proximal components of the carotid artery. Middle cerebral artery (MCA) and anterior cerebral artery (ACA)^1,2. Involvement of the retro vertebral circulation is rare. By definition, angiographic findings of progressive stenosis of the anterior circulation are bilateral in MMD patients, and unilateral findings are classified as Moyamoya syndrome (MMS). MMS is a secondary process that occurs in response to other disease processes^11,14.

Epidemiology:

Globally, the age of onset of MMD is quite bimodal, with the highest incidence in the first decade of life and a moderate peak between the ages of 20 and 30 years. It has a rib top. Surprisingly, there were geographic differences in gender distribution. The incidence of MMD in the foreign population has been reported to be higher in women than in men, with male to female ratios ranging from 1:1.1.1:2.2 in 8; However, the sex ratio is 1. No. #1 in China. For unknown reasons, MMD is relatively more common in East Asian countries such as Japan and Korea than in the Western Hemisphere^{23, 29}. MMD is most common in infants but can also occur in adults. This may be due to specific genetic differences in specific communities. About 10% of Moyamoya individuals are of Asian national origin. MMD can occur at any age, but is most prevalent twice in children aged 5 to 10 years and in adults aged 30 to 50 years^7,27. MMD is found worldwide, but is more common in East Asian countries; especially Korea, Japan and China. This may be due to specific genetic differences in specific communities. MMD usually occurs in people under the age of 20 in Japan. It is estimated to occur in 1 in 300,000 people in Japan^2,4,5.

For unknown reasons, MMD is relatively more common in East Asian countries such as Japan and Korea than in the Western Hemisphere. MMD is most common in infants but can also occur in adults. This may be due to specific genetic differences in specific communities. About 10% of Moyamoya individuals are of Asian national origin. MMD can occur at any age, but is most prevalent in children aged 5 to 10 years and twice in adults aged 30 to 50 years^4,7. MMD is found worldwide, but is more common in East Asian countries, especially Korea, Japan and China. This may be due to specific genetic differences in specific communities.MMD usually occurs in people under the age of 20 in Japan. It is estimated that 1 in 300,000 people in Japan will develop this disease^5,7,27. Moyamoya disease was originally identified in people of Japanese descent, but cases have been reported in Europe and the Americas as well as elsewhere in Asia. Most of the series documented in the Western Hemisphere include Asian patients. It contains a lot. Interestingly, the majority of patients in North America are acute cases, and recent studies show that less than 4% of cases in this population are maternal⁷.

Etiology:

10-15% of cases of Moyamoya disease (MMD) are familial, suggesting a genetic link. East Asian populations with the RNF213 gene on chromosome 17q25.3 are susceptible to MMD. In another report from Japan, the RNF213 variant (c.14576G) was found in 41 (95%) patients with familial MMD, 163 (79%) patients with sporadic MMD, and 283 (2%) normal controls notable. In a study of Han Chinese, Wu et al. showed that mutations in the RNF213 gene are associated with increased susceptibility to MMD¹². The etiology of the disease is still unknown. It is considered to have genetic potential because of its high incidence in Japan and Korea and a familial history in both Japanese and Caucasian populations^1,2. There is a recent report of an increased family history. This apparent increase may partly reflect the fact that the disease has been identified in asymptomatic patients through the widespread use of magnetic resonance imaging (MRI) and magnetic resonance angiography. A recent genome-wide search found an association of markers located on 3p24.2-26 with this disease^12,23. Another linkage study using a marker on chromosome 6, where the HLA gene is located, showed an association between the D6S441 marker and disease.HLA DNA typing also indicates that a disease is likely to have a genetic origin. An association with chromosome 17 has also been reported^17,19.

Moyamoya syndrome (MMS) is a separate entity when the disease is associated with other conditions such as:

· Arteriosclerosis

· Infection

· Hematologic status

· Vacuities and autoimmune disease

Pathology:

Many factors are thought to be involved in the development of moyamoya disease.

1) Fibroblast growth factor: considered a possible mediator of the angiogenic response. There is evidence that CSF-bFGF may be involved in the pathogenesis of disease¹.

2) Transformational growth Beta factor 1: (TGF beta 1), a factor involved in angiogenesis and connective tissue gene expression, was also increased in this disease.

3) Unknown Cerebrospinal Fluid Protein: It found in some patients with moyamoya disease. Further analysis of this protein may provide clues to the molecular mechanism of moyamoya disease¹⁶.

4) The Role of Prostaglandins: The role of prostaglandins in the pathogenesis of this disease has been studied. These studies show that moyamoya Cox2 arterial smooth muscle cells are activated and produce excessive PGE in response to inflammation¹⁰.

5) Possible Role of Infection: It possibly pathogenesis. Evidence is still inconclusive, but some studies suggest a link to Epstein-Barr virus infection.

6) Epstein-Barr Virus Infection: This was based on the increased presence of EBV DNA and antibodies in hospitalized moyamoya patients⁸.

Moyamoya type change is used when similar data are related to the underlying disease. Recently, the term has been questioned and it has been proposed to remove the term Moyamoya syndrome and replace it with "systemic disease with angiographic Moyamoya". Perhaps it will continue until there is an explanation⁹.

Pathophysiology:

Role of RNF213 in MMD Pathophysiology:

The exact function of RNF213 is unknown. Recent in vivo experiments using genetically engineered RNF213 mice addressed the underlying mechanism of the RNF213 SNP in the development of MMD pathology. Targeted disruption of RNF213 did not induce MMD in RNF213-deficient mice under normal conditions or Kanoke et al. Knockin created his own mouse^16,18 R4859K, exon 60, from an MMD patient. However, these mice did not develop MMD under normal conditions. Cerebral blood flow and moyamoya metabolism. The prevalence of moyamoya is directly related to cerebral blood flow. This has been shown in previous studies using xenon-133 inhalation.

Cerebral Blood Flow and Metabolism in Moyamoya: Cerebral blood flow decreased the most in the frontal lobe, and blood flow was relatively normal in the temporal and occipital lobes²⁶. Blood flow decreased in all areas after hyperventilation. Studies using positron emission tomography have shown increased total blood volume and increased transit time, especially in the striatum. It has been shown to impair the cerebrovascular response to hypercalcemia. These changes were reversed after reperfusion surgery¹³. PET studies also showed that vasodilation was within the normal range after hyperventilation ceased. This can lead to steely reactions that exacerbate hypoperfusion. These studies help understand the consequences of chronic cerebrovascular disease. Xenon CT was used for preoperative and postoperative evaluation. These studies have been found to be relevant for angiographic studies and are considered the best for examining the basal ganglia and posterior circulation^1,2,19. Contrast-enhanced diffusion-weighted imaging and perfusion magnetic resonance imaging were used to study ischemic episodes. Additionally, many studies have shown that cerebral blood flow decreases with age¹⁸.

Figure 2. Mechanism of moyamoya disease

Sign and symptoms:

Moyamoya disease causes different symptoms in adults and children, the first symptom is usually a stroke or recurrent transient ischemic attack (TIA), particularly symptomatic but also associated with these symptoms. Bleeding in the brain (hemorrhagic stroke). Early recognition of symptoms is very important to avoid serious complications such as stroke^4,12.

Signs and symptoms of moyamoya disease, which is characterized by reduced blood flow to the brain, include:

1. Headache.

2. Forfeiture.

3. Weakness, numbness or numbness in the face, arms or legs. It is usually located on one side of the body.

4. Decreased vision.

5. Difficulty speaking or understanding others (aphasia).

6. Development delays.

7. Transient isschemic attack or TIA (short stroke-like symptoms).

8. Involuntary movements²⁸.

Diagnosis:

In 1996, guidelines for the diagnosis and treatment of spontaneous obstruction of Willis' ring (moyamoya disease, MMD) were published^{1, 2, and 4}. Carotid, proximal ACA and/or MCA; ii) abnormal vasculature near stenotic occlusive arterial phase lesions; iii) the symptoms are bilateral. Moyamoya disease is usually diagnosed by a neurologist who specializes in the disorder. A specialist will check symptoms, family history, medical history, etc., and perform a physical examination. Several tests are usually needed to diagnose moyamoya disease and its underlying condition. Inspections include:

· Magnetic Resonance Imaging (MRI): MRI uses powerful magnets and radio waves to take detailed images of the brain. Doctors inject a contrast agent into blood vessels to view arteries and veins and highlight blood flow (magnetic resonance angiography)¹⁴.

· Computed tomography (CT): A CT scan uses a series of x-rays to create detailed images of the brain. This test cannot diagnose the early stages of moyamoya disease, but it can help identify abnormal blood vessels.

· Cerebral angiography: In cerebral angiography, doctors insert a long, thin tube (catheter) into a blood vessel in the groin and use x-rays to direct it to the brain. The contrast agent adapts to the shape of the blood vessels so they are more visible on x-rays^{9, 24}.

· Positron emission tomography (PET) or single photon emission tomography (SPECT): In this test, a small amount of harmless radioactive material is injected and a radiation detector is placed over the brain. PET provides visual images of brain activity. SPECT measures blood flow to different areas of the brain^23,29.

· Electroencephalography (EEG): EEG uses a series of electrodes attached to the scalp to monitor electrical activity in the brain. EEG abnormalities are often observed in children with moyamoya.

· Transcranial Doppler: Surgical transcranial Doppler uses sound waves to visualize the head and sometimes the neck. Doctors can use this test to evaluate blood flow in neck vessels¹².

Treatment:

There is currently no evidence that medications can slow or reverse the progression of MMD. Current medical treatment for MMD treats only clinical symptoms such as ischemia and hemorrhage with anticoagulants or haemostatic agents. Although the 2012 Japanese guidelines recommend the use of antiplatelet agents for the treatment of ischemic MMD, the risk of bleeding remains².

1) Role of antithrombotic agents in moyamoya disease: Antithrombotic therapy consists of platelet aggregation inhibitors, anticoagulants and thrombolytic agents. The main principle of antithrombosis is to prevent thrombosis. It is less certain that ischemic events in moyamoya disease are associated with thrombus formation^10,
13. The etiology of this disease is not thromboembolism, which causes cerebral ischemia in patients with moyamoya disease, but deficiency of cerebral blood flow due to progressive stenosis of the corresponding artery. The role of antithrombotic therapy in preventing ischemia in moyamoya disease is also not absolute.

2) Role of Antihypertensive Therapy in Moyamoya Disease: Japanese guidelines for the management of moyamoya disease recommend administration of antihypertensive drugs during the acute phase of intracranial hemorrhage to control blood pressure and prevent hematoma expansion. However, the target blood pressure for the acute phase of intracranial hemorrhage is unknown. During the acute phase of intracranial hemorrhage in moyamoya patients, guidelines assume that systolic and diastolic blood pressures should be controlled below 180 mmHg and 105 mmHg, respectively, but clinical evidence is lacking^{11, 15}.

3) Role of Lipid-Lowering Therapy in Moyamoya Disease: The benefits of lipid-lowering treatment in moyamoya disease are unknown. Direct clinical trials of lipid-lowering therapy for moyamoya disease have not been conducted. Among these lipid-lowering drugs, statins are the only subgroup that helps prevent primary and secondary ischemic stroke in patients with suspected atherosclerosis. Indirect evidence from Church et al. We have shown that statins, the major lipid-lowering drugs used to treat atherosclerosis, can slow the progression of unilateral moyamoya disease. Japanese guidelines for the treatment of moyamoya disease do not recommend routine lipid-lowering therapy unless dyslipidemia is present. For patients with suspected stroke or atherosclerosis, it is reasonable to lower the recommended low-density lipoprotein (LDL) level to less than 100 mg/dL^18,23.

There are three types of surgical revascularization for MMD: 1) Direct revascularization 2) Indirect revascularization and 3) Combined revascularization. Superficial arterial MCA anastomosis is the most common method of direct revascularization. Superficial temporal artery-ACA or occipital artery-A if ischemic hypoperfusion occurs in the ACA or the blood-supplying region of the posterior cerebral artery. posterior cerebrum; Indirect revascularization is a surgical procedure based on various tissues used as a blood source, mainly for cerebral myoangiopathy, cerebral artery angiopathy, multibore surgery, cerebral dural artery angiopathy, brain dura including arterial conjunctival neuroangiopathy, and omental transplantation^17,
30. Combined revascularization is the combination of her two former revascularizations.A recent meta-analysis showed that direct or combined revascularization is appropriate for unstable adult patients with MMD characterized by symptomatic or hemodynamic instability^{24, 25}.

CONCLUSION:

Moyamoya disease is a very rare disease; the above review article main aim is all information about this moyamoya disease etiology, pathophysiology, diagnosis and treatment of this rare disease which is related to the cerebrospinal fluid which present in the blood. To provide the information about moyamoya disease is shown by the above review paper.

REFERANCE:

1. Gupta A, Tyagi A, Romo M, et al. Moyamoya Disease: A Review of Current Literature. Cureus. 2020; 12(8): e10141.DOI 10.7759/cureus.10141

2. Demartini Z Jr, Teixeira BCA. Koppe GL, Gatto LAM, Roman A, Munhoz RP. Moyamoya disease and syndrome: a review. Radiol Bras. 2022; 55 (1):31-37.

3. KB, Akhtar N, Syed NA, Shafqat S, Baig SM: Moyamoya disease: an elusive diagnosis. JPMA. 2003, 53 (4):160-162.

4. Jong S. Kim, et al. Moyamoya Disease: Epidemiology, Clinical Features and Diagnosis. 2015

5. Yongjun Wang and Jizong Zhao; A review on Epidemiology of Moyamoya disease in china: A nationwide hospital – based study; published by Elsevier Ltd. (http://creativecommons.org/licenses/by.nc.nd/4.0/).

6. Drs. Hann and Ahn; review on Incidence, Prevalence, and Survival of Moyamoya Disease in Korea; http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.113.004273/-/DCI.

7. Das S, Dubey S, Das S, Hazra a, pandit A, Ghosh R and Ray Bk (2022) Epidemiology of Moyamoya Angiopathy in Eastern India. Front. Neurol. 13: 837704.doi:10.3389/Fneur.2022.837704.

8. Menon G, Hegde A. Moyamoya disease. Arch Med Health Sci. 2019; 7: 224-32.

9. Kleinloog R, Regli L, Rinkel GJE, et al. Regional difference in incidence and patient charachetristics of moyamoya disease: a systematic review. Journal of Neurology, neurosurgery & Psychiatry 2012; 83: 531-536. (http://dx.doi.org/10.1136/jnnp-2011-301387)

10. Guliz Acker, Lucius Fekonja, Peter Vajkoczy; Surgical Management of moyamoya disease. Stroke. 2018; 49(2): 476-482. (http://doi.org/10.1161/STROKEAHA.117.018563)

11. Paritosh Pandey, Gary K Steinberg; Neurosurgical advances in the treatment of moyamoya disease. Stroke. 2011; 42(11): 3304-3310.

12. Kiyohiro Houkin, Masaki Ito, Sugiyama, Hideo Shichinohe, Naoki Nakayama, Ken Kazumata, Satoshi Kuroda. Review of past research and current concepts on the etiology of moyamoya disease. Neurologia Medica-Chirurgica. 2012; 52(5): 267-277.

13. Keisuke Ueki, Fredric B Meyer, James F Mellinger; Mayo Clinic Proceedings. 1994; 69(8): 749-757.

14. Miki Fujimura, Teiji Tominaga. Diagnosis of moyamoya disease: international standard and regional differences. Neurologia Medico-Chirurgica. 2015; 55(3): 189-193.

15. Stephanie Guey, Elisabeth Tournier-Lasserve, Dominique Herve, Manoelle Kossorotoff. Moyamoya disease and syndromes: from genetics to clinical management; the application of clinical genetics. 2015: 49-68.

16. Takeshi Mikami, Hime Suzuki, Katsuya Komatsu, Nobuhiro Mikuni. Influence of inflammatory disease on the pathophysiology of moyamoya disease and quasi-moyamoya disease. Neurologia medico-Chirurgica. 2019; 59(10): 361.

17. Eric J Arias, Colin P Derdeyn, Ralph G Dacey Jr, Gregory J Zipfel. Advances and surgical considerations in the treatment of moyamoya disease. Neurosurgery. 2014; 74(suppl_1): S116-S125,

18. Annick Kronenburg, Kees PJ Braun, Albert van der Zwan, Catharina JM Klijn. Recent advances in moyamoya disease: pathophysiology and treatment. Current Neurology and Neuroscience Reports. 2014; 14: 1-9.

19. Gosalakkal J A. Moyamoya Disease: A Review. Neurol India 2002; 50: 6-10. (hhtp://www.neurologyindia.com/text.asp?2002/50/1/6/1371).

20. KVNR, A. and KV, R. 2017. Moya Moya Disease- A review. Asian Journal of Pharmaceutical and Clinical Research. 2017; 10 (4): 14-20.DOI: hhtp://doi.org/10.22159/ajpcr.2017.v10i4.13453.

21. Ohkubo, K., Y., Inoue, H. et al. Moyamoya disease susceptibility gene RNF213 links inflammatory and angiogenic signals in endothelial cekks. Sci Rep. 2015; 5: 13191. http://doi.org/10.1038/srep13191.

22. Deng X, Zhang D, Zhang Y, Wang R, Wang B, Zhao J. J Clin Neurosci. 2017; 42.

23. Moyamoya disease with occlusion of bilateral vertebral arteries and the basilar artery fed by the collateral vessels of vertebral arteries. A Rare Case Report. 116–118.

24. Zhang H, Zheng L, Feng L. Epidemiology, diagnosis and treatment of moyamoya disease; Exp Ther Med. 2019; 17: 1977–1984.

25. Hishikawa T, Sugiu K, Date I. Moyamoya disease: a review of clinical research; Acta Med Okayama. 2016; 70: 229–236.

26. Surgical management of moyamoya disease. Acker G, Fekonja L, Vajkoczy P. Stroke. 2018; 49: 476–482.

27. Suzuki J and Takaku A. Cerebrovascular ‘moyamoya’ disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969; 20: 288–299.

28. Baba T, Houkin K and Kuroda S. Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry. 2008; 79: 900–904.

29. Hayashi T, Shirane R and Tominaga T. Additional surgery for postoperative ischemic symptoms in patients with moyamoya disease: The effectiveness of occipital artery-posterior cerebral artery bypass with an indirect procedure. Technical Case Report. Neurosurgery. 2009; 64: E195–E196.

30. Kim JS, Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis. Journal of Stroke. 2016

31. Wang G, Zhang X, Feng M, Liu X, Guo F, Efficacy of Surgical Treatment on the Recurrent Stroke Prevention for Adult Patients with Hemorrhagic Moyamoya Disease. The Journal of Craniofacial Surgery. 2017

Received on 15.05.2024 Revised on 07.12.2024

Accepted on 22.04.2025 Published on 14.05.2025

Available online from May 16, 2025

Res.J. Pharmacology and Pharmacodynamics.2025;17(2):115-120.

DOI: 10.52711/2321-5836.2025.00019

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.