eMedicine Specialties > Neurology > Pediatric Neurology

Moyamoya Disease: Treatment & Medication

Author: Roy Sucholeiki, MD, Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital
Coauthor(s): Jasvinder Chawla, MBBS, MD, MBA, Associate Professor of Neurology, Director of Neurology Residency Training Program, Director of Clinical Neurophysiology Laboratory, Assistant Director of Neurology Clerkship Program, Department of Neurology, Loyola University Medical Center
Contributor Information and Disclosures

Updated: Nov 6, 2008

Treatment

Medical Care

Pharmacologic therapy for moyamoya disease (MMD) is disappointing. Therapy is directed primarily at complications of the disease.

  • If intracerebral hemorrhage has occurred, then management of hypertension (if present) is imperative.
  • In cases of severe stroke, ICU monitoring is indicated until the patient's condition stabilizes.
  • If the patient has had an ischemic stroke, consider anticoagulation or antiplatelet agents.
    • The rationale behind anticoagulation and antiplatelet agents is to prevent further strokes, especially in stenotic vessels where further infarction can occur if occlusion progresses.
    • These medications are not approved by the Food and Drug Administration (FDA) specifically for use in MMD, so the decision to treat with anticoagulants, ie, heparin (and in some cases, warfarin for long-term anticoagulation), or antiplatelet agents (eg, aspirin) rests on the following: angiogram findings, severity of stroke, and risk/benefit analysis by physicians who are experienced in stroke treatment.
  • Consultation with an experienced neurologist helps guide appropriate care.
  • Angiogram can determine the extent of occlusion or stenosis.

Surgical Care

Patients with moyamoya disease who present for treatment while symptoms are evolving have a better prognosis than those who present with static symptoms (which probably indicate a completed stroke).

  • Various surgical procedures have been used: superficial temporal artery–middle cerebral artery (STA-MCA) anastomosis, encephaloduroarteriosynangiosis (EDAS), encephaloduroarteriomyosynangiosis (EDAMS), pial synangiosis, and omental transplantation.
  • These procedures can be divided into 2 groups depending on whether they involve direct or indirect anastomosis. Which of these is most effective remains controversial. Sufficient evidence suggests that surgical revascularization procedures result in some symptomatic benefits along with demonstration of improved blood flow. Direct and/or combined procedures provide improved vascularization. However, data proving sustained or improved long-term outcomes is insufficient.
  • STA-MCA anastomosis is very difficult in children younger than 2 years because of the small diameter of the STA. In these cases, EDAS may be more suitable. This procedure sometimes has failed because of poor revascularization. Hoffman suggested that this is due to the presence of atrophy and a layer of spinal fluid between the pia and arachnoid tissue.3 Division of this arachnoid membrane and placement of the STA directly on the pial membrane helps to avoid the problem.
  • In cases of EDAS failure, EDAMS can be considered.

Consultations

  • Initial neurologic consultation is imperative. A neurologist can document neurologic deficits, consider the differential diagnosis, conduct testing to validate suspected etiologies, and commence medical management as indicated.
  • Neuroradiology consultation is needed to help determine the extent of radiologic testing needed (ie, MRA vs conventional angiography). Based on the results of these tests, a neurosurgeon can decide if surgical intervention would be helpful.

Activity

Rehabilitation with physical therapy, occupational therapy, and speech therapy should be considered depending on the neurologic impairment.

  • The extent of therapy can range from bedside to full comprehensive inpatient rehabilitation. The latter would include physical, occupational, speech, and cognitive therapy.
  • The condition of the patient including active comorbidities dictate involvement in rehabilitation therapy.

Medication

Drug therapy for moyamoya disease (MMD) depends on the particular manifestations of the disease.

For hemorrhage, therapy revolves around management of hypertension (if present).

For ischemic stroke, anticoagulation with heparin or warfarin may be considered. Safety and efficacy have not been fully established with these drugs, and careful analysis of risk and benefits is needed. These drugs could be useful if thrombosis of vessels is present, but they do not alter the natural history of the disease and they considerably increase the risk of hemorrhage with large strokes.

The same considerations are true for aspirin and other antiplatelet agents.

Treatment with anticoagulation or antiplatelet agents should be pursued only after consultation with a neurologist who is experienced in stroke management.

Anticoagulants

These agents are given for prevention of further thrombosis and potential infarction of the brain. CAUTION: Anticoagulation is of unproven benefit in ischemic stroke associated with MMD. This therapy therefore is considered empirical.


Heparin

Administered IV, and frequently given with initial bolus in cardiac situations. In stroke, bolus not recommended. Target dose aimed at maintaining aPTT 1.5-2 times control.
CT scan of brain must be done prior to any anticoagulant use to rule out preexisting intracranial hemorrhage.

Adult

50 U/kg/h IV initially, followed by continuous infusion of 15-25 U/kg/h; increase dose by 5 U/kg/h q4h prn using aPTT results

Pediatric

Not established

Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity

Documented hypersensitivity; conditions that predispose to bleeding; evidence of active bleeding such as severe strokes, presence of intracranial hemorrhage, positive stool blood test findings, or suspected bleeding elsewhere

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In neonates, preservative-free heparin recommended to avoid possible toxicity (ie, gasping syndrome) of benzyl alcohol, which is used as preservative; caution in severe hypotension and shock; patients should be monitored closely by providers with experience in managing anticoagulation


Warfarin (Coumadin)

Administered orally and used if long-term anticoagulation needed. INR followed with target range of 2-3.
CT scan of brain must be done prior to any anticoagulant use to rule out preexisting intracranial hemorrhage.

Adult

5-15 mg/d PO qd for 2-5 d; adjust dose according to desired INR

Pediatric

Not established

Drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate
Medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac

Documented hypersensitivity, severe liver or kidney disease, open wounds or GI ulcers, conditions that predispose to bleeding

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Do not switch brands after achieving therapeutic response; caution in active TB or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis; patients need careful periodic monitoring by personnel who are experienced in using anticoagulants; caution in children whose activity level may be a risk factor for trauma and subsequent hemorrhage

Antiplatelet agents

These agents can be considered to help prevent future ischemic strokes. As with anticoagulation, aspirin is of unproven benefit in MMD; its use is considered empirical.


Aspirin (Anacin, Ascriptin, Bayer Aspirin)

Efficacy in preventing stroke relies on its inhibitory effect on platelet function. This presumably would help prevent thrombus formation and propagation.

Adult

81-650 mg PO qd

Pediatric

Not established; 2-5 mg/kg/d PO typically used

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; other coagulation or bleeding disorders; concurrent anticoagulants; severe anemia; asthma; preexisting gastric ulcer disease; positive test for stool blood; due to possible association with Reye syndrome, do not use in children (<16 y) with flu

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease

More on Moyamoya Disease

Overview: Moyamoya Disease
Differential Diagnoses & Workup: Moyamoya Disease
Treatment & Medication: Moyamoya Disease
Follow-up: Moyamoya Disease
References
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Further Reading

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Keywords

moyamoya disease, MMD, arterial occlusive disease, primary cerebral, puff of smoke, Graves disease, thyrotoxicosis, leptospirosis, tuberculosis, aplastic anemia, Fanconi anemia, sickle cell anemia, lupus anticoagulant, Apert syndrome, Down syndrome, Marfan syndrome, tuberous sclerosis, Turner syndrome, von Recklinghausen disease, Hirschsprung disease, atherosclerotic disease, coarctation of the aorta and fibromuscular dysplasia, cranial trauma, radiation injury, parasellar tumors, hypertension

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Contributor Information and Disclosures

Author

Roy Sucholeiki, MD, Director, Comprehensive Seizure and Epilepsy Program, The Neurosciences Institute at Central DuPage Hospital
Roy Sucholeiki, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, and American Neuropsychiatric Association
Disclosure: UCB Pharma Honoraria Speaking and teaching

Coauthor(s)

Jasvinder Chawla, MBBS, MD, MBA, Associate Professor of Neurology, Director of Neurology Residency Training Program, Director of Clinical Neurophysiology Laboratory, Assistant Director of Neurology Clerkship Program, Department of Neurology, Loyola University Medical Center
Jasvinder Chawla, MBBS, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Neurology, Division of Pediatrics, Department of Pediatrics, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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