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Minocycline Prevents Focal Neurological Deterioration Due to Cerebral Hyperperfusion After Extracranial-Intracranial Bypass for Moyamoya Disease

Fujimura, Miki MD*,‡; Niizuma, Kuniyasu MD*; Inoue, Takashi MD; Sato, Kenichi MD*; Endo, Hidenori MD*; Shimizu, Hiroaki MD*; Tominaga, Teiji MD*

doi: 10.1227/NEU.0000000000000238
Research-Human-Clinical Studies

BACKGROUND: Cerebral hyperperfusion (CHP) is a potential complication of superficial temporal artery–middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD), and optimal postoperative management has not yet been established. Minocycline, a neuroprotective antibiotic agent, plays a role in blocking matrix metalloproteinase 9 (MMP-9), which contributes to edema formation and hemorrhagic conversion after cerebral ischemia-reperfusion. Patients with MMD have been shown to have increased serum MMP-9 levels.

OBJECTIVE: To examine the effect of minocycline on the prevention of postoperative CHP after STA-MCA anastomosis for MMD.

METHODS: N-isopropyl-p-[123I]iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 109 hemispheres in 86 consecutive patients with MMD (ages, 9-69 years; mean, 37.2 years). Postoperative systolic blood pressure was strictly maintained at lower than 130 mm Hg in all 109 surgeries. The most 60 recent hemispheres were managed by the intraoperative and postoperative intravenous administration of minocycline hydrochloride (200 mg/d). The incidence of focal neurological deterioration (FND) due to CHP was then compared with that in 36 patients undergoing 49 surgeries managed without minocycline.

RESULTS: FND due to CHP was observed in 4 operated hemispheres in patients treated without minocycline (4/49, 8.16%), and in none in the minocycline-treated group (0/60) (P = .0241). Multivariate analysis revealed that minocycline administration (P < .001), surgery on the left hemisphere (P = .031), and a smaller recipient artery diameter (P < .001) significantly correlated with FND due to CHP.

CONCLUSION: The administration of minocycline with strict blood pressure control may represent secure and effective postoperative management to prevent symptomatic CHP after STA-MCA anastomosis for MMD.

ABBREVIATIONS: CBF, cerebral blood flow

CHP, cerebral hyperperfusion

EC-IC, extracranial-intracranial

EDMS, encephaloduromyosynangiosis

FND, focal neurological deterioration

123I-IMP-SPECT, N-isopropyl-p-[123I]iodoamphetamine single-photon emission computed tomography

MCA, middle cerebral artery

MMD, moyamoya disease

MMP-9, matrix metalloproteinase 9

MRA, magnetic resonance angiography

SPECT, single-photon emission computed tomography

STA-MCA, superficial temporal artery–middle cerebral artery

Author Information

*Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan;

Department of Neurosurgery, National Hospital Organization, Sendai Medical Center, Sendai, Japan

Correspondence: Miki Fujimura, MD, PhD, Department of Neurosurgery, Tohoku University Graduate School of Medicine, 1.1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. E-mail:

Received August 06, 2013

Accepted October 25, 2013

Copyright © by the Congress of Neurological Surgeons