CASE REPORT Electroconvulsive Therapy in a Patient With Moyamoya Syndrome Erica Ghignone, MD,* Lisa Rosenthal, MD,* Robert Brett Lloyd, MD, PhD,* Samdeep Mouli, MD,† and Stephen Dinwiddie, MD* Abstract: We report on a 30-year-old woman diagnosed with moyamoya syndrome resulting from sickle cell disease who developed catatonia and was successfully treated with electroconvulsive therapy (ECT). Neuroimaging revealed severe tandem narrowing of the left internal carotid artery with diminished cerebral blood flow, moderate narrowing of the right supraclinoid aspect of the right internal carotid artery, and associated numerous lenticulostriate collaterals bilaterally, consistent with moyamoya. The patient presented with mutism; posturing; immobility; stupor; withdrawal; refusal to eat, drink, or speak; and staring, supporting a diagnosis of catatonia. It initially responded to a lorazepam challenge; however, a complicated hospital course and deterioration of the patient's condition, including septic shock, delirium, and continued catatonic symptoms, led to the pursuit of ECT to treat her symptoms. We discuss the risks involved with the administration of ECT in a patient with fragile cerebral vasculature and the successful treatment of catatonia in this patient without resultant stroke or cerebral hemorrhage. Key Words: electroconvulsive therapy, moyamoya syndrome, sickle cell disease, catatonia (J ECT 2015;31: e14–e16) M oyamoya syndrome is a chronic cerebrovascular disease characterized by progressive bilateral stenosis of the intracranial portions of the internal carotid arteries. As the arteries narrow and blood flow decreases, many small, fragile collaterals (“moyamoya vessels”) form, leading to the characteristic “puff of smoke” appearance on neuroimaging; the disease was first described in 1957.1,2 If the condition occurs alone, it is referred to as “moyamoya disease”; in 10% to 20% of cases, it is caused by sickle cell disease (SCD), neurofibromatosis type 1, cranial irradiation, or Down syndrome or (less commonly) by hyperthyroidism, renal artery stenosis, giant cervicofacial hemangiomas, or congenital cardiac malformations, in which case it is called “moyamoya syndrome.” Primary psychiatric presentation appears rare, but the ischemic and hemorrhagic consequences of the condition can cause a variety of neuropsychiatric manifestations such as depressed mood, personality changes, cognitive impairment, and psychosis marked by negative symptoms, all of which may be mistaken for primary psychiatric disease.3,4 CASE REPORT By age 30 years, Ms H, an African American woman with no psychiatric history but who had a history of SCD, had had many sickle cell crises and had developed secondary hemochromatosis From the Departments of *Psychiatry and Behavioral Sciences, and †Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL. Received for publication February 11, 2014; accepted April 10, 2014. Reprints: Erica Ghignone, MD, Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, 446 E. Ontario St, 7th Floor Suite 200, Chicago, IL 60611 (e‐mail: Erica.ghignone@northwestern.edu). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000151 e14 www.ectjournal.com from numerous transfusions, dilated cardiomyopathy resulting from the chronic anemia of SCD, and oxygen desaturations during the sleep-wake cycle and had sustained microinfarcts in the left frontal and left subinsular white matter. Her latest crisis had required nursing home placement for pain control via intravenous narcotics for more than a month. During a period of several days, she was noted to have stopped eating, drinking, and swallowing and became only minimally responsive, showing little spontaneous movement. Workup at an outside hospital was negative for infection, and her symptoms were attributed to catatonia. She reportedly improved slightly and was discharged back to the nursing home but worsened within a week and was transferred to our facility. On admission, the patient was afebrile and normotensive, with a normal pulse and respiratory rate and 99% oxygen saturation. Physical examination revealed a patient lying in bed, perfectly still, eyes open to slits; she blinked to visual threat but did not acknowledge the examiner, did not follow commands, and did not withdraw to painful stimuli including nail bed pressure or sternal rub. Complete blood cell count showed hemoglobin of 6.7 g/dL and hematocrit of 20.1%. Electrolyes and creatinine were within normal limits. Electroencephalogram results were normal. Computed tomography scan of the brain did not reveal any acute changes. Magnetic resonance imaging of the brain and magnetic resonance angiography (MRA) of the brain showed left and right internal carotid artery (ICA) stenosis, along with decreased caliber of the right posterior cerebral artery and multiple collaterals adjacent to both middle cerebral arteries consistent with moyamoya syndrome (Figs. 1–3). Mutism; posturing; immobility; stupor; withdrawal; refusal to eat, drink, or speak; and staring supported a diagnosis of catatonia, and she responded promptly to a lorazepam challenge. After receiving a total of 3 mg administered intravenously, she sat up in bed, was able to speak in full sentences, and requested to eat and drink. However, despite treatment with 2 mg of lorazepam 3 times a day, during the following week, catatonic signs reemerged. During her hospital stay, Ms H experienced an acute decompensation overnight. She became febrile to 39.3°C; became hypotensive to 82 mm Hg systolic and 31 mm Hg diastolic; and developed an uptrending white blood cell count, creatinine level, and lactate level, requiring transfer to the medical intensive care unit. She developed septic shock due to Acenitobacter and coagulase-negative staphylococci, the source of which was believed to be her central venous catheter. Vancomycin, aztreonam, and amikacin were started, and with volume resuscitation and blood transfusion, she was able to return to hemodynamic stability. Subsequently, she developed Clostridium difficile colitis and began to exhibit low mood, persecutory delusions, and auditory hallucinations along with waxing and waning changes in her level of alertness. Electroencephalogram showed mild encephalopathy. She remained very difficult to engage, at times responding only to sternal rub, and refused to eat and drink. Electroconvulsive therapy Journal of ECT • Volume 31, Number 1, March 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Journal of ECT • Volume 31, Number 1, March 2015 ECT in a Patient With Moyamoya Syndrome FIGURE 3. Sagittal MRA showing collateralization (blue and black arrows). Note the difference in the vessel caliber when comparing anterior circulation (ICA: black arrow) with posterior circulation (vertebrobasilar: double red arrows); the vertebrobasilar system is normal in caliber, whereas the ICA system, including the proximal M1, is stenosed. This sparing of posterior distribution is classic for moyamoya. FIGURE 1. Three-dimensional reconstructed images of MRA of the head. Image shows severe tandem stenoses of the intracranial left ICA at the level of the genu and supraclinoid segments (white arrows). (ECT) was recommended, and after a lengthy discussion, her mother (the patient’s decisional substitute) agreed to proceed. A petition for involuntary treatment was filed, but because of the patient’s deteriorating medical status, treatment was started emergently, as allowed under the Illinois Mental Health Code. Treatments were administered using a Thymatron System IV device, with bilateral electrode placement and 100% charge delivered at 0.75-millisecond pulse width and 50 Hz; for anesthesia, the patient received 1 mg/kg of methohexital and 0.6 mg/kg of succinylcholine. In addition, before treatment, she received 500 mcg/kg of esmolol for improved blood pressure and heart rate control. Because of the severity of her clinical condition, initial treatment settings were maximized (as described); threshold titration was not performed (thus decreasing any risk associated with subconvulsive stimuli), and atropine was not administered. Response to treatment was rapid, with substantial improvement noted after the first treatment. After her fifth treatment, she had fully returned to baseline: she was fully alert, conversant, and functionally limited only by her cardiomyopathy. She was able to return to the skilled nursing facility, where she received 2 more treatments, then elected to discontinue them. In the ensuing 2 months, the patient was readmitted twice for pain control in the context of continued sickle cell crisis, but catatonic signs did not recur. Three months after her initial presentation, Ms H was brought to the emergency department after becoming lethargic earlier that day. Electroencephalogram showed generalized slowing, and she was found to be in high-output cardiac failure. Cardiac function continued to deteriorate, and after a series of medical setbacks ultimately culminating in sepsis, the patient died. DISCUSSION FIGURE 2. Three-dimensional reconstructed images of MRA of the head. Image demonstrates the diminutive caliber of the right anterior cerebral artery A1 and A2 segments (green arrows). Also seen is moderate narrowing of the supraclinoid segment of the right ICA (red arrow). There are an increased number of vessels suggestive of collateral formation. One notable collateral vessel is a prominent posterior communicating artery filling the left middle cerebral artery, resulting in the reconstitution of blood flow (white arrow). To our knowledge, this is the first known case of catatonia resulting from moyamoya syndrome, and the second in which ECT has been safely administered. Although most commonly associated with mood disorders, the syndrome of catatonia can manifest as a nonspecific complication of a wide variety of medical and neurological disorders ranging from infectious disease, nonconvulsive status epilepticus, and metabolic disturbances including uremia and metabolic ketoacidosis to autoimmune disorders such as systemic lupus erythematosus and even stroke.5 Regardless of the cause, the treatment of catatonia remains the same; benzodiazepines and ECT are the primary treatment modalities, along with treatment of the underlying illness.6,7 However, given the nature of the underlying vascular pathology, moyamoya syndrome may present particular risks with ECT. The condition is characterized by thickening of the intima of the intracranial portions of the internal carotid arteries and their branches that leads to stenosis. As a compensatory mechanism for the narrowing of the vessels and diminished blood flow, small branches dilate and form collateral vessels. As the disease progresses, aneurysms form in these dilated arteries at the base of the brain, which then can rupture and hemorrhage. In addition, the © 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. www.ectjournal.com e15 Journal of ECT • Volume 31, Number 1, March 2015 Ghignone et al collateral vessels become occluded, which causes ischemic phenomena such as transient ischemic attacks and strokes.8 Given the fragility of the collateral vessels and the known risk for hemorrhage in this condition,3 the rapid increase in blood pressure and cerebral blood flow associated with ECT could potentially be associated with increased risk for hemorrhagic stroke. However, there is at least 1 case report of a patient with unsuspected moyamoya syndrome who had ECT.9 In that case, although the patient developed a prolonged posttreatment delirium, it does not seem that the delirium was caused by the moyamoya syndrome; rather, the pattern of collateral vessels and aneurysmal dilations was incidentally identified via angiogram as part of the evaluation for the cause of the patient's delirium. The delirium was concluded to be the clinical manifestation of occult ischemic lesions of the basal ganglia. That patient received a total of 4 ECT treatments, all before the diagnosis of moyamoya syndrome; head imaging (including computed tomography, magnetic resonance imaging/MRA of the brain) obtained after the completion of the ECT did not reveal any acute ischemic changes. In the case of Ms H, it was concluded that moyamoya syndrome had caused her catatonic symptoms, and ECT was ultimately necessary for their resolution. Knowing the risks involved with administering ECT in a patient with stenotic and fragile cerebral vasculature allowed us to take the necessary precautions to decrease the likelihood of any resultant cerebrovascular accidents. CONCLUSIONS We report a case of a woman with SCD that resulted in multiple systemic complications including dilated cardiomyopathy, hemochromatosis, stroke, and ultimately moyamoya syndrome. In the midst of a sickle cell crisis, the diminished blood flow to her brain was further decreased, likely the ultimate cause of the e16 www.ectjournal.com catatonic symptoms noted on admission. She initially responded to a lorazepam challenge, but the effect was not enduring. She became severely medically ill with bacteremia, requiring intensive care; underlying ischemic disease in addition to septic shock predisposed Ms H to delirium. Her presentation was complex because of a clinical picture of catatonia and supervening delirium that required ECT to fully resolve. The fragility of this patient's cerebral vasculature would be expected to significantly increase the risk for further cerebrovascular events in the context of ECT; however, this case demonstrates that, with proper precautions, the treatment can be delivered safely. REFERENCES 1. Takeuchi K, Shimizu K. Hypoplasia of the bilateral internal carotid arteries. Brain Nerve. 1957;9:37–43. 2. Suzuki J, Takaku A. Cerebrovascular “moyamoya” disease: disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20:288–299. 3. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009;360:1226–1237. 4. Lubman DI, Pantelis C, Desmond P, et al. Moyamoya disease in a patient with schizophrenia. J Int Neuropsychol Soc. 2003;9:806–810. 5. Daniels J. Catatonia: clinical aspects and neurobiological correlates. J Neuropsychiatr Clin Neurosci. 2009;21:371–380. 6. Fink M. Catatonia: a syndrome appears, disappears, and is rediscovered. Can J Psychiatry. 2009;54:437–445. 7. Unal A. Effective treatment of catatonia by combination of benzodiazepine and electroconvulsive therapy. J ECT. 2013;29:206–209. 8. Yamashita M, Oka K, Tanaka K. Histopathology of the brain vascular network in moyamoya disease. Stroke. 1983;14:50–58. 9. Gitig A, Merino JG, Hoffman L, et al. Moyamoya disease presenting as atypical post-ictal delirium after ECT in a woman with clinically silent putaminal infarcts. Einstein Q J Biol Med. 2000;17:190–193. © 2015 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.