Moyamoya disease: Causes, symptoms, diagnosis and treatments
Health experts reveal all you need to know about the causes, symptoms, diagnosis and treatments of Moyamoya disease
Moyamoya disease is defined as a rare idiopathic, progressive, bilaterally symmetrical arteriopathy of childhood, resulting in narrowing of distal ICA and proximal ACA/MCA with formation of collaterals looking like “puff of smoke” called moyamoya in Japanese and the first case report from India was reported by Dr Balasubramaniam while the first case of surgery for Moyamoya disease, Extracranial-intracranial bypass was reported by Dr Basant Misra in 1988. Moyamoya disease is more prevalent in oriental population than western population, probably related to genetic predisposition.
According to a recent literature review on East Asian countries, the prevalence and incidence of MMD is comparatively high in Japan, Korea, Taiwan and China, all having higher prevalence and incidence compared to West (Japan 6.03/100,000 and 0.56/100,000 in 2003, Korea having prevalence of 9.1/100,000 in 2008 and incidence of 2.3/100,000 in 2011 and China having a prevalence rate of 3.92/100,000 during 2000-2007). There is a slight female preponderance to male in most surveys for sporadic MMD though it is reported as 1:1 for familial MMD.
Majority are sporadic with approximately 10%-15% only having a positive family history however, there is 30-40 times more risk for developing MMD among family members. A genetic contribution is suspected due to a strong link with ethnicity and increased prevalence among first degree relatives and more recently, among East Asians, genome wide and locus specific studies identified RNF213 (ring finger protein) gene in the 17q25-ter region as a susceptibility gene for MMD.
In an interview with HT Lifestyle, Dr VR Roopesh Kumar, Senior Consultant and Lead - Neurosurgery at Apollo Proton Cancer Centre, shared, “A polymorphism in RNF213 variant p.R4810K is being strongly associated with familial MMD and is identified in 95% of familial patients with MMD and 79% of sporadic cases. This genetic abnormality correlates with the early-onset and severe forms of MMD thus serving as a predictive good biomarker. MMD has 80% to 90% concordance in monozygotic twins which clearly denotes a genetic mechanism.”
According to Dr VR Roopesh Kumar, Moyamoya disease (MMD) is a chronic progressive cerebral angiopathy involving anterior circulation characterised by bilateral stenosis internal carotid arteries (ICA) and its proximal branches with development of a fine network of abnormal compensatory collateral vessels subsequently. He said, “The characteristic angiographic pattern is the formation of collateral blood vessels giving the appearance of a “puff of smoke”, which is roughly translated as “Moya Moya” in Japanese. When such vasculopathy is associated with any secondary causes like down syndrome, cranial irradiation, sickle cell disease, neurofibromatosis type etc, it is termed as Moyamoya Syndrome (MMS).”
He added, “Majority are sporadic with approximately 10%-15% only having a positive family history. However, there is 30-40 times more risk for developing MMD among family members. There were two peaks of incidence, children at 5-14 years and another in adults between 35-50 years. Rare even in general population, the prevalence and incidence of MMD in families is not fully studied. In one North American surgical series, among pediatric patients with MMD treated between 1985 and 2015, only 3.4% of the cases were familial. The incidence of familial MMD was 6%–15.4% in Japan, 9.4% in China and 12% in Korea respectively according to one East Asian series.”
Dr VR Roopesh Kumar revealed, “In children, ischemic symptoms, especially transient ischemic attacks, are predominant and accounts for approximately 6% of pediatric strokes, with a peak incidence rate at 5–9 years and a second higher peak in adulthood. However, up to 30 % of these patients remained asymptomatic, especially in familial cases. Intellectual decline, seizures, and involuntary movements are also more common in this age group. In contrast, adult patients present more often with intracranial haemorrhage with greater propensity to develop intra ventricular haemorrhage. There is a risk of symptomatic MMD recurrence of about 18% in the first year after the initial presentation. This increases by 5% every year and has a 5-year cumulative risk of approximately 40%.”
Talking about the clinical presentation, Dr BK Misra, Head - Department of Neurosurgery and Gamma Knife Radiosurgery, Chief of Surgery at PD Hinduja Hospital and MRC at Mahim, said, “The clinical manifestation depends on rapidity and extent of vascular occlusion and effectiveness of collateral circulation. The presentation in children is usually Ischaemic, recurrent/ alternating episodes of focal neurologic deficit. Seizures and involuntary movements are also more common than adults. Adults usually present with a haemorrhage.” According to him, the common presentations are:
1. Transient Ischaemic Attack (TIA: transient neurologic deficit that recovers within 24 hours like paralysis or numbness of one limb or one side of body)
2. Infarction ( Stroke: persistent paralysis or numbness of one limb or one side of body, inability to speak or understanding)
Dr BK Misra said, “MRI Brain with MR Angio of brain vessels is usually diagnostic. Further evaluation can be done by perfusion studies by CT, MRI or PET scan.”
Dr VR Roopesh Kumar elaborated, “The diagnosis of MMD is based on anatomical and functional aspects which include qualitative and non-qualitative imaging studies. Non-qualitative imaging techniques include different angiographies such as DSA, CT angiography (CTA), and magnetic resonance angiography (MRA). Digital subtraction angiography (DSA) continues to be the gold standard to confirm the diagnosis and in showing the dynamic vascular changes and excellent for disease staging as the Suzuki classification.”
He added, “Qualitative imaging techniques include Single-photon emission CT, PET, xenon-enhanced computed tomography (Xe-CT), perfusion CT, dynamic susceptibility contrast (DSC), and arterial spin labelling (ASL) MRI, Acetazolamide challenged ASL Perfusion studies and quantitative DSA (QDSA). CT and MR perfusion studies are easier to perform, practical and economical than SPECT/PET or Xe-CT. Acetazolamide-challenged ASL quantifies augmentation of cerebrovascular reserve (CVR), and this serves as a predictor for improvement after revascularization surgeries. The use of transcranial Doppler (TCD) can assess the mean arterial velocity and resistance index before and after surgery which is another method for ascertaining effectiveness of revascularization.”
Management and treatments available in India:
As per Dr BK Misra, the medical management includes Anticoagulant and Antiplatelet agent while the surgical management includes Revascularization procedures, Perivascular sympathectomy and Superior cervical ganglionectomy. Asserting that the mainstay and definitive treatment is some form of revasculariztion, he explained -
- Direct Revascularization:
Suturing one extracranial (commonly a scalp vessel) to a brain vessel, usually a terminal branch of middle cerebral artery. The various types of bypasses commonly employed are Superficial Temporal Artery to branch of Middle Cerebral Artery Bypass (STA-MCA) and uncommonly STA to Anterior Cerebral Artery (ACA), STA to Posterior Cerebral Artery (PCA) or Occipital Artery to PCA
- Advantages of Direct Revascularization
i) Immediate Revascularization
ii) Robust Revascularization
- Disadvantages of Direct Revascularization
i) Technically Demanding
ii) Availability of Donor Vessel
iii) Limited Revascularization outside anastomosis
iv) Hyperperfusion Syndrome
v) Short and Long-term Failure
- Indirect revascularization
Apposing a vascular donor tissue on the brain surface without any direct anastomosis between vessels.
i) Encephalo-duro-arterio synangioses (EDAS)/ Encephalo-duro-arterio-mayo synangioses (EDAMS)
ii) Encephalo-mayo synangioses (EMS)/ Encephalo-Fascio synangioses (EFS)
iii) Multiple Burr Holes
iv) Omental transposition
- Advantages of Indirect Revascularization
i) Suitable for even small children
ii) Unsuitable donor Vessel
iii) Technically Easy
iv) Shorter ICU stay
v) Robust and Long-term Revascularization
vi) Good Post operative Neurologic Outcome
- Disadvantages of Indirect Revascularization
i) Revascularization slow
ii) Risk of Stroke during Latency Period
There are many centres in India where all the above treatments are available and early diagnosis and appropriate treatment helps in improving the natural history of the disease. Bringing his expertise to the same, Dr VR Roopesh Kumar insisted, “Currently no specific therapeutic strategy is effective in preventing or reversing the vascular changes associated with MMD. Hence, the treatment is aimed at preventing the recurrence of ischemic events, controlling symptoms, and managing long term ischemic insult to brain.” He highlighted -
- Medical management:
The effectiveness of medical management in preventing recurring strokes/haemorrhages and halting the progress of the disease and chronic ischemia is not very encouraging. The options are with antiplatelet and antiepileptics which will not alter the progression.
- Endovascular Management:
There is no proper endovascular modalities for this disease in particular, though it has now been the mainstay treatment for other Cerebro vascular diseases.
- Surgical management:
Revascularization surgery has shown more favourable results in preventing recurring strokes and to mitigate the ill effects of chronic ischemia when compared to conservative management. As Cerebrovascular reserve (CVR) inversely correlates with stroke risk in children with Moyamoya disease, revascularization is an effective strategy which augments CVR.
- Direct Revascularization techniques: (Vascular Bypass)
The ECA-to-ICA bypass is a direct revascularization surgical procedure in which the distal branches of the ECA branch, such as the Superficial Temporal Artery (STA) is bypassed and anastomosed to distal M4 cortical branches of the Middle cerebral artery (MCA). This aims at re-establishing blood flow immediately to an under-perfused territory, which has a success rate of around 87 to 100% as in studies done based on serial angiograms and published worldwide. The direct techniques prove beneficial by providing an immediate vascular supply. This procedure is quite challenging especially in young children as the vessel calibre is very narrow and requires significant surgical expertise in microvascular anastamosis. Hence, these procedures are undertaken only in few specialized apex neurosurgical centres in the country like AIIMS, PGI, NIMHANS, Sri Chitra Tirunal Institut, Apollo Proton Centre etc.
- Indirect Revascularization techniques: (Synangiosis)
Indirect techniques are more popular as they are technically less demanding and are undertaken in many institutes. They are dependent on complex physiological process of angiogenesis by forming connections between adjacent damaged vessels. New anastomosis is created between external and internal circulations, which will take time for hemodynamically significant revascularization. Even though indirect techniques have its advantages, it may take months to years before full revascularization is achieved.
- Encephalo duro arterio synangiosis (EDAS)- STA is placed into direct contact with the cerebral cortex without anastomosis.
- Encephalo-myo-synangiosis (EMS)- The highly vascularized temporalis muscle is placed on direct contact with the surface of the brain.
- Encephalo duro Arterio Myo Synangiosis (EDAMS)- Combination of both EDAS with EMS where both the artery and the temporalis muscle is placed on top of the brain parenchymal surface for facilitating angiogenesis.