Moyamoya Moyamoya Disease Double Trouble Jan Boerke, ACNP AACN Brunch January 24, 2015 Moyamoya - puff of smoke in Japanese Describes the look of the tangle of tiny vessels formed to compensate for the blockage in the internal carotid artery. The internal carotid arteries are the most common arteries to become blocked, but can also affect the middle and anterior cerebral arteries. First described in 1957 in Japan Because of the blockage, the blood vessels start to develop new pathways to find ways to get blood to the brain. Collateral network Epidemiology Most prevalent in Japanese and Asian populations In Japanese population 0.35 to 0.54 per 100,000 population 7% to 12% of cases in Japan considered familial 1
Epidemiology European population estimated to be one tenth of the incidence in the Japanese population In the United States, 0.086/100,000 persons (about 1 in a million) Females affected nearly twice as often as males Pathogenesis Poorly understood Genetic and acquired factors have been implicated. Pathogenesis Genetic factors Recent studies have focused on genetic factors in the pathogenesis of Moyamoya disease Associated with many genetically transmitted disorders, including neurofibromatosis, Down syndrome, sickle cell anemia, and collagen vascular diseases including Marfan syndrome, Ehler-Danlos syndrome Genetic Abnormalities on chromosomes 3, 6, 8, and 17 have been linked to familial (inherited) moyamoya disease. A specific abnormality in a gene that codes for a smooth muscle protein called alpha actin (ACTA2) has been found in patients with familial (inherited) and nonfamilial forms of moyamoya disease. This ACTA2 abnormality is called a susceptibility gene for moyamoya disease and is also linked to early onset coronary artery disease. Hereditary A hereditary factor has been proposed, because the incidence of familial cases in Asian populations has been reported as high as 12% Pathogenesis - Acquired History of inflammation in the head and neck region may be associated with the development of moyamoya disease. One series showed approximately two thirds of patients had previous inflammatory disease. This inflammation model has been reproduced in dogs - foreign protein injected into the carotid artery led to the formation of intracranial vessels with a moyamoya pattern. Irradiation - the dose of radiation capable of causing this is unknown and the time between treatment and disease onset is highly variable, ranging from months to decades. Arteriosclerosis 2
Pathophysiology Progressive cerebrovascular disorder Stenosis or occlusion of bilateral supraclinoid internal carotid arteries Unlike atherosclerosis, the artery wall actually overgrows inward to constrict the artery. Autopsy reports in moyamoya patients show prominent intimal thickening, which in some cases is due to lipid deposition and edema. The ICA is divided into 8 segments 1. Cervical 2. Ascending petrous 3. Horizontal petrous 4. Ascending cavernous 5. Horizontal cavernous 6. Clinoid 7. Opthalmic 8. Terminal Moyamoya commonly involves both intracranial hemispheres, but unilateral disease has been reported 40% of patients who initially present with unilateral findings later progress to develop disease on the unaffected side. Development of lenticulostriate hypertrophy Presenting symptoms Adults Japanese population - Adults most often present with a hemorrhagic stroke. (42%) US population does not bear this out. 20% of US patients present with hemorrhage In the United States, most adults and children present with ischemic symptoms 3
Children Hemorrhage It is extremely rare for children (< 18 years old) to present with hemorrhage 2.8%) Predominantly present with TIAs or ischemic strokes (68%) as shown in the largest current report of pediatric moyamoya patients Can be induced by crying, coughing, or straining Hemorrhage from fragile collateral vessels Often accompanied by intracranial aneurysms Possibly because of the increased blood flow and hemodynamic stress in the abnormally dilated collateral vessels. May explain the higher incidence of intracranial hemorrhage in adult patients with moyamoya disease Stanford series of adults 89% presented with ischemia 7% with hemorrhage 4% with both ischemic and hemorrhagic symptoms In 70% to 80% of patients, the hemorrhage occurs deep in the basal ganglia, thalamus, and ventricular wall. Natural History Peak age of onset in the Asian population is bimodal Early peak occurring in the first decade of life Second peak in the fourth decade of life In one Asian series the mean age of diagnosis was 5 years for the early peak and 36 years for the later peak. Natural History Without surgery, the majority of individuals with Moyamoya disease will experience mental decline and multiple strokes because of the progressive narrowing of arteries. May have speech deficits (usually aphasia), sensory impairments, involuntary movements, and vision problems. The natural history of untreated moyamoya disease is poor: the rate of major deficit or mortality over the 2 years following diagnosis is 73% in children, and the prognosis is similarly poor in adults, 66%. Evaluation Cerebral angiogram demonstrates Stenosis or occlusion of supraclinoid ICA Lenticulostriate hypertrophy For surgical planning - allows identification of superficial temporal arteries (STAs) of reasonable size, indicating that a superficial temporal-to-middle cerebral artery bypass can be performed. 4
Treatment Medical management of moyamoya disease includes: maintenance of hydration use of antiplatelet agents like aspirin or Plavix moderate control of hypertension Use caution when treating moyamoyainduced hypertension. Low blood pressure can lead to a stroke. Despite medical management, the incidence of subsequent stroke in all patients with moyamoya disease ranges from 60 to 80%. Medical vs Surgical Tx. In symptomatic patients High incidence of stroke in medically treated patients. Hallemeier et al reported a series of 34 patients with Moyamoya, 22 bilateral and 12 unilateral. In medically treated hemispheres, the 5-year risk of recurrent ipsilateral stroke was 65% after the initial symptom, whereas in surgically treated hemispheres, the 5-year risk of perioperative and subsequent ipsilateral stroke was 17% (P=0.02). Surgery Consequently, the gold-standard treatment for moyamoya disease is revascularization surgery, a procedure that increases blood flow to the affected region of the brain. The first STA-MCA bypass for moyamoya disease was performed by Yasargil in 1972 Surgery aimed at revascularization of the hemispheres either by direct or indirect bypass techniques Indications for surgical treatment Combination of patient s symptoms and radiographic evaluation. Symptoms related to ischemia or previous hemorrhage. Progressive neurologic deficits, such as cognitive decline or progressive seizures Evaluation prior to Surgery Cerebral angiography evaluates size of the superficial temporal arteries (STAs) If < 1 mm not adequate size for direct bypass Evaluates moyamoya vessels 5
CT perfusion With and without diamox (acetazolamide) The initial CTA indicates baseline cerebral blood flow and identifies areas of low perfusion. Acetazolamide causes vasodilatation If the blood vessels are already maximally dilated, the diamox will not cause further vasodilation A second CTA after administration of diamox evaluates the reserve capacity of cerebral blood flow. Impaired reserve or actual "steal" phenomenon after acetazolamide suggests these brain regions are at high risk for subsequent infarct. Xe-CT CBF maps in a patient with Moyamoya disease. Vagal A et al. AJNR Am J Neuroradiol 2009;30:876-884 2009 by American Society of Neuroradiology Xe-CT CBF maps in a patient with Moyamoya disease. A, Baseline. B, After ACZ administration. Baseline scan (A) shows reduced CBF in the bilateral ACA and anterior watershed areas (areas 1, 2, 19, and 20, asterisk). After ACZ, there is a robust increase in the CBF, indicating a normal cerebral reserve in these territories. In the left posterior MCA and the left posterior watershed territories (areas 13 15, arrows). there is reduced baseline flow with decreased augmentation of CBF after ACZ, indicating poor cerebral reserve STA-MCA Bypass In anecdotal series, STA-MCA markedly improves: Ischemic symptoms Cerebral blood flow (CBF) measurements Hemodynamic reserve Clinical outcome STA-MCA bypass Patients are positioned with the head above the heart to reduce venous cerebral congestion. Hyperventilation avoided due vasoconstrictive effects Mild hypothermia (32-34 C) and barbiturates are used routinely to provide a cerebral protective effect during occlusion times. Mean arterial pressure kept in the normal to high range. Patients should be volume expanded to prevent ischemic events. Vasoconstrictive agents such as epinephrine should not be used during scalp infiltration. Intraoperative monitoring with EEG and somatosensory evoked potentials (SSEPs) provides early detection of ischemic changes. 6
After the scalp is shaved, a Doppler ultrasound probe and the preoperative angiograms are used to identify the location of the STA, which is then marked out with a marking pen. Following sterile preparation, an incision is made, beginning over the zygoma The STA is identified and skeletonized using sharp dissection When necessary, a sterile Doppler probe can be used to confirm the course of the STA. It is desirable to leave a cuff of tissue around the artery itself. This reduces direct trauma to the artery, decreases vasospasm of the vessel, and allows the surgeon to grasp the donor segment without injuring the vessel. Smaller branches of the artery are bipolar coagulated; larger branches are isolated and ligated. The length of the artery required depends on the distance from the artery to the graft site. Donor vessels should be selected with an outer diameter 1 mm Smaller vessels have higher occlusion rates, provide less blood flow, and are more difficult to anastomose. Optimal recipient middle cerebral artery (MCA) branches have outer luminal diameters 1 mm. An M3 or M4 MCA branch is preferred. A small piece of sterile plastic is placed beneath the segment of the MCA at the anastomosis site as a "high visibility" backfield. A temporary aneurysm clip is placed on the proximal STA, and the distal tip of the exposed vessel is ligated and cut. 7
Blood flow through the STA can be tested by transiently removing the proximal temporary aneurysm clip. The lumen of the STA is then irrigated with heparinized saline to minimize clot formation within the donor vessel. The distal portion of the STA vessel is trimmed to the appropriate length, based on location of the recipient vessel, and the soft tissue cuff is removed from the distal 3 to 5 mm as preparation for the anastomosis. The distal end of the donor vessel is cut in an oblique fashion. Small microvascular clamps then are placed on each side of the recipient vessel to prevent bleeding during the anastomosis. The recipient vessel is cut in a diamond-shaped fashion using a microscissors. The anastomosis is performed under the microscope using 10-0 monofilament suture. The intimal layer must be included with each interrupted stitch, but significant narrowing of the anastomotic site should be avoided. Temporary clips are then removed, first from the MCA branch, and then from the proximal STA. Total MCA branch occlusion times typically are 20 to 30 minutes. Once the anastomosis is complete, a Doppler ultrasound may be used to test patency. The dura is carefully closed to avoid compromising the STA. The bone flap also is trimmed to minimize any pressure on the donor vessel. Temporalis and scalp closure then proceeds in the usual fashion. Intra-operative imaging Indocyanine green (ICG) emits near-infrared fluorescence when excited by near-infrared light. After completion of the anastomosis, ICG is injected, excited by near-infrared light, and the bypass is visualized 8
ICG imaging Indocyanine Green ICG Post-operative Management Hemodynamic control is the primary goal of postoperative management. BP goal is 120-160 Hypertension may result in excessive bleeding at the anastomotic site. Hemorrhage can occur from increased perfusion of the brain Hyperperfusion Injury Causes transient or permanent neurological deficits. Well known in carotid endarterectomy and highflow bypasses; however, has been described in low-flow STA-MCA bypasses. More likely with high flow bypass such as with radial artery Pathologically, it occurs due to a rapid increase in blood flow in chronically ischemic regions of the brain. Hyperperfusion Management MRI does not show hemorrhage or infarct/diffusion lesions Patients have neurological deficits such as aphasia, dysarthria, orofacial apraxia, or sensorimotor loss. Important to recognize this syndrome because the treatment for it is the opposite of that of ischemia. A patient with postoperative ischemia despite a patent graft requires an increase in blood pressure and perfusion. A patient with symptomatic hyperperfusion requires tight control and lowering of blood pressure. The diagnosis is usually made with SPECT scan following the STA-MCA bypass or sometimes with other perfusion studies such as CT perfusion or MR perfusion 9
Hypotension Conversely, hypotension may cause graft occlusion resulting in clinical ischemia. In such cases, an emergent angiogram and graft revision may be necessary. Aspirin suppository is given in the OR as soon as drapes are removed Aspirin 325 mg daily is continued indefinitely Indirect bypass Placement of vascularized tissue supplied by the branches of external carotid artery on the brain to stimulate angiogenesis and collateral vessels in the brain. The ischemic brain tissue naturally causes blood vessels to connect between the transplanted tissues and ischemic arteries on the surface of the brain. This process restores blood flow to the affected area. Although indirect revascularization procedures have been found to be very beneficial and safe in children, their efficacy in adult moyamoya patients has been more controversial. Indirect Bypass Encephaloduroarteriosynangiosis Encephaloduroarteriosynangiosis Pial synangiosis Encephalomyosynangiosis Burr Holes Encephalo Duro Arterio Synangiosis 10
Encephaloduroarteriosynangiosis (EDAS), also known as Pial Synangiosis. Alternatives to the STA-MCA bypass can be used to augment blood flow to the brain. In encephaloduroarteriosynangiosis, the superficial temporal artery is first dissected out as for an STA-MCA bypass, but is left in continuity. The dura is then opened in a linear fashion, and the artery is placed over the exposed cortex. Initial reports indicated that the vessel could be placed over the arachnoid, but further studies show that improved collateral flow can be obtained by opening the arachnoid and allowing the STA to contact the pia. Encephaloduroarteriosynangiosis The soft tissue cuff of the STA then is sewn to the edge of the dura using 5-0 suture in a running fashion. Over time, angiogenesis results in the formation of small arterial vessels to the brain Advocates of EDAS maintain that this procedure does not involve temporary occlusion of an MCA branch and is technically easier to perform. In addition, EDAS can be used in cases where there is not a suitable donor or recipient vessel, and it can also be used in conjunction with a STA-MCA bypass New cortical vessels can be seen as early as 2 weeks after EDAS. Encephalomyosynangiosis (EMS). Temporalis muscle on the side of the head is dissected free Frontotemporal craniotomy is performed Dura is incised and arachnoid layer is opened Temporalis muscle is tucked under the bone and laid in contact with the brain surface Dura is laid over the muscle and secured to the edge of the temporalis muscle Over time, new vessels form between the bloodrich muscle and the brain. Encephalomyosynangiosis (EMS). Neovascularization occurs from the muscle tissue to the adjacent brain to supplement blood flow. Like EDAS, the EMS is easier to perform than the STA- MCA bypass, can be performed without identifying a recipient vessel, and can be combined with the STA- MCA bypass. However, this procedure has been associated with an increased risk of seizures. Several series have shown that EMS improves the clinical condition of patients as well as angiographic filling of the MCA vessels in 70% to 80% of cases. Direct vs indirect bypass Ishikawa et al. compared STA-MCA bypass (48 procedures) with indirect revascularization methods (16 procedures), such as encephaloduroarteriosynangiosis in pediatric moyamoya patients Showed that the incidence of postoperative ischemic events was significantly reduced in the direct bypass group (10%) compared to the indirect group (56%, p < 0.01 ). They concluded that direct revascularization is the procedure of choice over indirect revascularization whenever possible. Burr Holes Multiple burr holes are placed in the skull to allow for growth of new vessels into the brain from the scalp. 11
Follow Up Care Case study Repeat angiogram at 1 year Angiography and MRI studies often reveal a reduction in moyamoya vessels that closely parallels improvement in symptoms Patient is a 34-year-old female admitted to OSF Saint Francis Medical Center with a right basal ganglia hemorrhage History of Neurofibromatosis 1 Presented with left hemiparesis Cerebral angiogram demonstrated right Moyamoya disease with significant lenticulostriate hypertrophy. She underwent right extracanial/intracranial bypass, STA-MCA bypass And right encephalodurosynagiosis After the bypass was completed the dural flaps were released and inverted over the surface of the brain for dural synangiosis. The bone flap was reapproximated using multiple plates and screws. A sizable bony window was fashioned at the inferior aspect of the flap for the graft. 3 day hospital stay. Discharged home. 1 month follow up doing well. No deficits. Had resumed all usual duties other than return to work. Returned to work as pre-school assistant following 1 month appointment. 1 year angiogram Interval maturation of the right STA to MCA bypass with exuberant high flow to the right MCA territory predominantly involving the posterior division of the right middle cerebral artery. No evidence of any stenosis of the bypass anastomosis. 12
Case Study #2 52 year old female History of strokes starting in Spring 2010 with seizure disorder. Referred to Dr. Klopfenstein in January 2011 for evaluation of MCA stenosis because of the multiple right sided ischemic events. The patient states she has had a few significant strokes and multiple small strokes At the time of her initial consultation she demonstrated residual left sided weakness, which she felt was gradually worsening. 1-20-11 angio - Greater than 95% stenosis or near-complete occlusion of the proximal right M1 segment There is misery perfusion to the right cerebral hemisphere via collaterals from right anterior cerebral artery and the right posterior cerebral artery CTP - Mildly impaired right MCA perfusion with intact cerebral reserve. Right M1 stenosis Left normal caliber M1 2-18-14 Angio Moyamoya-type syndrome with unilateral highgrade stenosis of the right M1 segment of greater than 90 to 95% with hypertrophy of the right lateral lenticulostriate arteries. This is associated with misery perfusion and dural leptomeningeal recruitment Demonstrated progression of the moyamoya syndrome from her previous cerebral angiogram 3-20-14 - CTP Post Diamox images demonstrate an overall decrease in mean transit time to the right cerebral hemisphere with mild improvement in blood flow and blood volume. No redistribution. 5/16/14 - Right Superficial Temporary Artery to Middle Cerebral Artery Bypass 4 day hospital stay. Discharged home. Good strength in bilateral upper and lower extremities. Able to ambulate in the hallways with a wheeled walker. 13
One month follow up Awake, alert, and oriented except to the specific date. Right sixth nerve palsy present, which is chronic. Otherwise extra ocular movements are intact. She denies double vision. Mild left facial weakness secondary to her previous stroke. Five minute recall was two out of three. Serial sevens she did slowly, using her fingers, and accurately. She was able to spell the word world forwards but not backwards. No pronator drift. Strength is 5/5 in bilateral upper and lower extremities. Bibliography NINDS Moyamoya Disease Information Page, National Institute of Neurologic Disorders web page. Downloaded Neurosurgical Advances in the Treatment of Moyamoya Disease Paritosh Pandey, MD; Gary K. Steinberg, MD, PhD. Stroke 2011; 42: 3304-3310. Surgical Management of Moyamoya Disease Steven D. Chang, M.D., and Gary K. Steinberg, M.D., Ph.D. Downloaded Questions? 14