Moyamoya Disease and other Cerebral Vasculopathies

Diseases arising as a result of inflammation or degeneration of blood vessel may be referred to as a vasculopathy. There are particular sub-types of vasculopathy that may benefit from microvascular surgery to reconstruct blood flow to the brain.

Cerebral Vasculopathies

Cerebral vasculopathies is a collective term for a group of diseases where blood vessels, particularly small and medium sized arteries within the brain, become narrowed at intervals or occluded. There are a variety of causes for such changes in the vessels. Infections such as the Varicella virus may produce a vasculopathy resulting in stroke. Certain single gene mutations trigger clinical syndromes that may include the cerebral vasculopathy. One example is Fabry Disease where a mutation of the GLA gene impairs the action of an enzyme (Alpha-galactosidase A) resulting in disordered celll metabolism itself affecting the blood vessels of many organs including the brain. These vasculopathies affect the smallest arteries and rarely require neurosurgical involvement save in their diagnosis when biopsy of nervous tissue may be helpful.

When a vasculopathy affects intermediate sized arteries this may render the vessels fragile and thus prone to tearing (dissection) or rupture. It may also impair blood flow to the brain in which case reconstructive surgery to divert additional blood flow may be considered.

Moyamoya Disease

Moyamoya disease is a rare and progressive vasculopathy that selectively and primarily effects the internal carotid arteries as they enter the cranial cavity at the base of the skull. It is most commonly found in orietala and South East Asian populations but may be encountered around the world in its primary and secondary forms. The word "Moyamoya" is Japanese meaning "puff of smoke" and intended to describe the appearance of the nebulous cloud of collateral vessels that develop in response to the narrowing of the normal parent vessels.

Primary Moyamoya or Moyamoya Disease occurs in isolation and is unrelated to any other systemic condition or insult. It occurs in about 0.54 per 100,000 of the Japanese population. It is about ten time less common in western society although its prevalence may be under-estimated by a failure to investigate and diagnose certain strokes.

Catheter angiogram showing severe stenosis of both internal carotid arteries in a patient with Moyamoya Disease

The exact cause is not known with certainty. Chemical mediators which drive the formation of new blood vessels are found more frequently in the cerebrospinal fluid of patients with Moyamoya Disease. This may itself be a respose to a chronic lowering of oxygen delivery to the brain tissue. and these mediators , most importantly Vascular Endothelial Growth Factor (VEGF), interacting with vascular progenitor cells in the circulating blood drive the formation of the clouds of collateral vessel which give the name. A mutation RNF213 gene, p.R4810K has been implicated in MMD OF East Asian patients but has not been found in Western cohorts to date.

The presence of these factors driving new blood vessel formation which is exploited the surgical treatment of Moyamoya disease described below to develop additional brain blood flow.

When the characteristic vasculopathy of Moyamoya Disease develops in association with another systemic condition or physiological insult, this is termed Moyamoya Syndrome or Secondary Moyamoya. Radiotherapy fields that include the supraclinoid internal carotids may induce narrowing of the vessels many years after the initial treatment. This has been encountered whether proton beam, electron or photon particles are delivered and whether external beam radiation or internal radiotherapy (brachytherapy).

Neurofibromatosis type 1, a genetic condition affecting connective tissue development may produce a Moyamoya syndrome. It is also seen with trisomy 21 (Down syndrome). Perhaps the most common secondary Moyamoya vasculopathy seen in our practice complicates Sickle Cell Disease, itself an inherited blood disorder mostly affecting people of sub-saharan African descent.

Neurofibromatosis type 1, a genetic condition affecting connective tissue development may produce a Moyamoya syndrome. It is also seen with trisomy 21 (Down syndrome). Perhaps the most common secondary Moyamoya vasculopathy seen in our practice complicates Sickle Cell Disease, itself an inherited blood disorder mostly affecting people of sub-saharan African descent.

Clinical Presentation

Moyamoya may present with ischaemic stroke (nerve cells die for sufficient oxygen) or haemorrhagic stroke (nerve cells are physically disrupted by bleeding). If a stroke develops it is usually obvious from the patterns of symptoms that something serious is amiss e.g weakness of a limb. The onset of symptoms may be more subtle however and stroke is not always inevitable. Function in nerves may become impaired by insufficient delivery of oxygen when demand is placed upon them. This may produce "mini-strokes" quickly reversible deficits that initially resemble a stroke. Migraine, psychological symptoms, movement disorders and intellectual impairment may also be presentations


Medical Treatment

Platelets are blood cells that at as first-responders to bleeding, clumping together to form a temporary plug at the site of bleeding allowing time for a more durable blood clot to be formed. Drugs that inhibit platelet function have an established role in the prevention of stroke where it results from blood clots blocking small blood vessels. The best known of these drugs is Aspirin and its use has been advocated in Moyamoya disease where there has not been previous haemorrhage.

There are no high-quality randomised control trials of Aspirin to prevent stroke in Moyamoya disease at present. The research studies which are available are conflicting on its ability to prevent disability. It probably does not reduce mortality from Moyamoya disease in the long-term.

Direct Surgical Revascularisation

Direct surgical revascularisation utilises a donor blood vessel from the scalp and joins it to a recipient blood vessel on the surface of the brain. The most commonly performed procedure is called a Superficial Temporal Artery to Middle Cerebral Artery (STA-MCA) bypass. The evidence to support it as reducing the future risk of stroke is strongest in those who have experienced a haemorrhagic Moyamoya presentation. There is one prospective randomised control trial suggesting a 2-3 fold reduction in future stroke after successful surgery . This benefit is not seen however until about 12 months after the surgery and there is a slightly elevated risk of stroke around the time of the procedure itself.

STA to MCA bypass CT angiogram

The evidence to support any surgical treatment as a means to prevent stroke in those who are asymptomatic or who have symptoms unrelated to bleeding is less certain with no good-quality research to indicate a favourable risk-benefit balance. The procedure is offered particularly in cases where an impairment of cerberovasculr reserve can be empirically demonstrated . There are ongoing registry studies that will hopefully provide better data in due course.

Indirect Surgical Revascularisation

Indirect surgical revascularisation exploits the microenvironment of the brain surface which in Moyamoya Disease is rich in chemical mediators that drive the formation of new blood vessels and the presence of vascular progenitor cells. Tissue which retains its own blood supply, when placed in apposition to the brain surface can facilitate the growth of new blood vessels that slowly join with and contribute to the brains native circulation.

Suitable tissues to act as such conduits include the superficial temporal artery itself, sutured to the brain surface without interrupting its supply of blood to the scalp (pial-arterio-synangiosis). The covering of the brain (dura) may be used (dural-arterio-synangiogsis), a section of chewing muscle at the side of the skull (myo-arterio-synangiosis) or both in combination (myo-dural-arteriosynagiosis). Vascularised connective tissue (pericranium) on the surface of the skull also afford s an effective conduits . Tissues have been used from more remotely also including omentum which is a fattty apron of tissue in the abdomen. The in-growth of blood vessels is slow and as a result any increase in blood flow to the surface of the brain.

We favour indirect revascularisation in children where recipient vessels may be very small but it has proven a reliable revascularisation option in adults on occasion. The two approaches may be very effectively combined in adult patients without adding significantly to procedural risk.

Steno-occlusive Disease and Flow Dependent Ischaemia

Narrowing or occlusion of the intracranial vessels resulting from "hardening of the arteries" (atherosclerosis) will occasionally present with symptoms resulting from reduction of blood flow to the brain when demand arises for more blood flow. Where the circulations ability to increase flow in response to such demands is impaired there is said to be a reduced cerebrovascular reserve.

Superficial temporal artery to middle cerebral artery bypass

While such impairment may portend an increased risk of stroke for some clinical trials have not demonstrated that increasing the flow with revasularisation surgery will reduce that risk consistently and safely. As these trial results emerged there were also improvements in medical drug therapies and alternative survival and endovascular approaches to extra-cranial carotid disease have emerged (carotid endarterectomy, carotid tenting). There may remain rare cases of low dependent ischaemia that could benefit form such surgery with objective evidence of impaired reserve demonstrated by specialised imaging.

Where narrowing of the carotid results from injury such as that caused after radiotherapy revascularisation may be considered particularly in young patients with demonstrably impaired reserve and symptoms. This is a rare indication and the evidence base for benefit again is likely to remain weak for the foreseeable future. A detailed discussion of the potential drawbacks as well as the benefits is advisable.