Association of Bypass Surgery and Mortality in Moyamoya Disease.

Background Patients with moyamoya disease (MMD) have a high risk of stroke or death. We investigated whether extracranial to intracranial bypass surgery can reduce mortality by preventing strokes in patients with MMD. Methods and Results This nationwide retrospective cohort study encompassed patients with MMD registered under the Rare Intractable Diseases program via the Relieved Co-Payment Policy between 2006 and 2019, using the Korean National Health Insurance Service database. Following a 4-year washout period, landmark analyses were employed to assess mortality and stroke occurrence between the bypass surgery group and the nonsurgical control group at specific time points postindex date (1 month and 3, 6, 12, and 36 months). The study included 18 480 patients with MMD (mean age, 40.7 years; male to female ratio, 1:1.86) with a median follow-up of 5.6 years (interquartile range, 2.5-9.3; mean, 6.1 years [SD, 4.0 years]). During 111 775 person-years of follow-up, 265 patients in the bypass surgery group and 1144 patients in the nonsurgical control group died (incidence mortality rate of 618.1 events versus 1660.3 events, respectively, per 105 person-years). The overall adjusted hazard ratio (HR) revealed significantly lower all-cause mortality in the bypass surgery group from the 36-month landmark time point, for any stroke mortality from 3- and 6-month landmark time points, and for hemorrhagic stroke mortality from the 6-month landmark time point. Furthermore, the overall adjusted HRs for hemorrhagic stroke occurrence were beneficially maintained from all 5 landmark time points in the bypass surgery group. Conclusions Bypass surgery in patients with MMD was associated with a lower risk of all-cause and hemorrhagic stroke mortality and hemorrhagic stroke occurrence compared with nonsurgical control.

Long-term follow-up results in 142 adult patients with moyamoya disease according to management modality.

BACKGROUND: To clarify the most beneficial treatment of the management modality based on our experience with adult moyamoya disease (MMD). METHODS: From 1998 to 2010, clinical results of 142 patients (ischemic, 98; hemorrhagic, 44) with adult MMD were investigated according to management modality. Revascularization surgery (direct, indirect, and combined bypass) was performed in 124 patients. We observed the clinical course of 18 patients who were treated conservatively. Clinical outcome, angiographic features, hemodynamic change, and incidence of recurrent stroke were investigated pre- and postoperatively. RESULTS: In patients with ischemic MMD, direct and combined bypasses were more effective treatments to prevent recurrent ischemic stroke than indirect bypass surgery (P < 0.05). In patients with hemorrhagic MMD, rebleeding was less likely to occur in patients who had undergone bypass surgery. However, no significant difference was observed in the rebleeding rate between patients with and without revascularization surgery (P > 0.05). An angiogram after bypass surgery comparing the extent of revascularization and reduction of moyamoya vessels in patients treated with direct, indirect, and combined bypass showed a significant difference (P < 0.05) in favor of direct and combined bypass. Postoperative angiographic changes and SPECT results demonstrated significant statistical correlation (P < 0.05). CONCLUSION: Revascularization surgery was effective in further ischemic stroke prevention to a statistically significant extent. Direct and combined bypasses were more effective to prevent recurrent ischemic stroke than indirect bypass. However, there is still no clear evidence that revascularization surgery significantly prevents rebleeding in adult MMD patients. More significant angiographic changes were observed in direct and combined bypasses compared with indirect bypass.

Motor-evoked potential confirmation of functional improvement by transplanted bone marrow mesenchymal stem cell in the ischemic rat brain.

This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

Ischaemic stroke after acute intracranial haemorrhage in patients with moyamoya disease: six new cases and a short literature review.

BACKGROUND: We report six new cases of ischaemic stroke after cerebral haemorrhage in patients with moyamoya disease (MMD) and analyse their clinical and radiological characteristics, together with cases reported in the literature, to deduce the mechanism of cerebral infarct. METHODS: Six (2%) of 246 patients with MMD who were admitted to our hospitals between 1993 and 2009 suffered cerebral infarct after intracranial haemorrhage. Ten patients identified in the literature with the PubMed search engine were also included in this study. All the ischaemic lesions in these 16 patients were analysed according to their location, size, and number and were compared according to the spatial relationship between the haemorrhage and infarct, as follows: (1) anterior vs posterior involvement, (2) cortical vs subcortical involvement, (3) watershed vs non-watershed infarct, (4) small vs large infarct, (5) single vs multiple infarct, and (6) adjacent vs distant involvement. RESULTS: Acute synchronous multiple brain infarcts occurred in six (38%) patients and recurrent infarcts in three patients (19%). Cerebral infarcts had mainly cortical (72%), anterior (66%), and distant involvement (75%) and were large (69%) and non-watershed (66%). Adjacent infarct had significantly anterior involvement (P < 0.05), and distant infarcts tended to have cortical involvement. Non-watershed infarcts had significantly cortical involvement (P < 0.05). Watershed infarcts tended to be large. Vasospasm was confirmed either pathologically or angiographically in two patients with large cerebral infarcts. CONCLUSIONS: We suggest that thromboembolism or vasospasm plays a crucial role in the pathogenesis of cerebral infarction after acute intracranial haemorrhage in patients with MMD.

Comparison of the effect of decompressive craniectomy on different neurosurgical diseases.

BACKGROUND: Many previous studies have reported that decompressive craniectomy has improved clinical outcomes in patients with intractable increased intracranial pressure (ICP) caused by various neurosurgical diseases. However there is no report that compares the effectiveness of the procedure in the different conditions. The authors performed decompressive craniectomy following a constant surgical indication and compared the clinical outcomes in different neurosurgical diseases. MATERIALS AND METHODS: Seventy five patients who underwent decompressive craniectomy were analysed retrospectively. There were 28 with severe traumatic brain injury (TBI), 24 cases with massive intracerebral haemorrhage (ICH), and 23 cases with major infarction (MI). The surgical indications were GCS score less than 8 and/or a midline shift more than 6 mm on CT. The clinical outcomes were assessed on the basis of mortality and Glasgow Outcome Scale (GOS) scores. The changes of ventricular pressure related to the surgical intervention were also compared between the different disease groups. FINDINGS: Clinical outcomes were evaluated 6 months after decompressive craniectomy. The mortality was 21.4% in patients with TBI, 25% in those with ICH and 60.9% in MI. A favourable outcome, i.e. GOS 4-5 (moderate disability or better) was observed in 16 (57.1%) patients with TBI, 12 (50%) with ICH and 7 (30.4%) with MI. The change of ventricular pressure after craniectomy and was 53.2 (reductions of 17.4%) and further reduced by 14.9% (with dural opening) and (24.8%) after returning to its recovery room, regardless of the diseases group. CONCLUSIONS: According to the mortality and GOS scores, decompressive craniectomy with dural expansion was found to be more effective in patients with ICH or TBI than in the MI group. However, the ventricular pressure change during the decompressive craniectomy was similar in the different disease groups. The authors thought that decompressive craniectomy should be performed earlier for the major infarction patients.

Ruptured right posterior inferior cerebellar artery aneurysm associated with hypoplasia of the right vertebral artery and both internal carotid arteries.

The authors report an extremely rare case of a ruptured saccular aneurysm of the right posterior inferior cerebellar artery (PICA) associated with hypoplasia of bilateral internal carotid arteries (ICAs) and the right vertebral artery (VA). The aneurysm was successfully treated by clipping of the aneurysm itself using a lateral suboccipital approach. The aetiology of hypoplastic ICAs and right VA is uncertain, but the associated distal aneurysm from the right PICA appears to have developed most likely due to a coexistent congenital vessel wall anomaly of the cerebral arterial structure.

Cranioplasty effect on the cerebral hemodynamics and cardiac function.

BACKGROUND: Cranioplasty is usually performed for aesthetic, protective and patient comfort reasons. The objective of this study is to examine the effects of cranioplasty on the cerebral hemodynamics and cardiovascular system. METHODS: Twenty-seven patients who had undergone cranioplasty after extensive skull bone removal to prevent uncontrollable intracranial hypertension were included in this study. Arterial blood flow velocities in the middle cerebral artery (MCA) and internal carotid artery (ICA) were assessed by transcranial doppler (TCD). The cardiac functions were evaluated using the echocardiogram. And cerebral blood flow were measured by perfusion CT. FINDINGS: The blood flow velocity at the MCA ipsilateral to the cranioplasty was decreased from 50.5 +/- 15.4 cm/s preoperative to 38.1 +/- 13.9 cm/s following cranioplasty (p < 0.001) and from 33.1 +/- 8.3 cm/s to 26.4 +/- 6.6 cm/s at the ICA (p < 0.001). The stroke volume was increased from 64.7 +/- 18.3 ml/beat, to 73.3 +/- 20.4 ml/beat (p < 0.001), while the cardiac output and mean arterial blood pressure were unchanged. The cerebral blood flow was increased from 39.1 +/- 7.2 ml/100g/min to 44.7 +/- 8.9 ml/100g/min on the cranioplasty side (P = 0.05). CONCLUSIONS: Cranioplasty can get rid of the atmospheric pressure on the brain and increase the cerebral blood flow as well as improve the cardiovascular functions. A skull defect should be corrected, because cranioplasty has not only aesthetic or protective effects but also improves the cardiovascular functions.

Simple excision and periosteal reattachment for the treatment of calcified cephalhematoma. Technical note.

Until now, calcified cephalhematoma has been treated by excision of the lesion and the use of an onlay autograft. The authors report their use of a less complicated alternative, simple excision and periosteal reattachment, in a 3-month-old male infant. They excised the calcified cap of cephalhematoma and reattached the periosteum to the exposed bone surface instead of using an onlay autograft technique. A follow-up CT scan demonstrated a smooth skull contour and good cosmetic appearance. The authors note that this is the first report of the successful use of simple excision and periosteal reattachment for the treatment of a case of calcified cephalhematoma in which there was a depressed area after the calcified cap was removed. They conclude that in cases of calcified cephalhematoma it may be unnecessary to perform a complicated cranioplasty with bone harvested from the top of the calcification.

Surgical results in pediatric moyamoya disease: angiographic revascularization and the clinical results.

OBJECTIVE: We retrospectively reviewed the pediatric patients with moyamoya disease (MMD) who underwent bypass surgery at our institution to compare the surgical results according to the surgical procedures. PATIENTS AND METHODS: There were 24 total patients (age range: 2-15 years; mean age: 8.2 years). Twelve patients underwent encephalo-duro-arterio-synangiosis (EDAS) on 16 sides, 5 patients underwent encephalo-duro-arterio-myo-synangiosis (EDAMS) on 8 sides and 7 patients underwent combined superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis with EDAMS (STA-MCA-EDAMS) on 12 sides. The postoperative results were evaluated between 4 months and 5 years following surgery in terms of the angiographic revascularization and the clinical outcome. RESULTS: EDAMS, regardless of the combined STA-MCA anastomosis, was significantly effective for achieving a good extent of the postoperative angiographic revascularization as compared with simple EDAS (P<0.05). STA-MCA-EDAMS tended to be better with respective to the relief of preoperative ischemic symptoms as compared with simple EDAS, although there was no significant statistical difference. CONCLUSION: These results suggest that EDAMS with or without the combination of STA-MCA anastomosis was very useful for the formation of collateral circulation in comparison with simple EDAS for treating the pediatric patients with MMD, although these findings were not well correlated with the clinical outcomes.

Sudden cortical blindness in an adult with moyamoya disease.

BACKGROUND: We report a case of an adult with MMD who presented initially with left visual field defect that had suddenly progressed to bilateral cortical blindness 1 year and 9 months later. CASE DESCRIPTION: A 33-year-old male presented with visual blurring and mild right hemiparesis that developed suddenly. He was regarded as having MMD based on an imaging study. An inverted encephalodurogaleosynangiosis using the left occipital artery and inverted encephaloduroarteriogaleosynangiosis with the parietal branch of the superficial temporal artery were done. The postoperative course was uneventful and without any complication. Several months later, he visited again because of sudden bilateral blindness preceded by repeated transient blindness in both eyes for 4 days. The right posterior temporal artery, which was well visualized at the time of the first postoperative follow-up angiography, was no longer seen on repeated 4-vessel angiography. Biochemical analysis including prothrombin and thrombin time, activated partial thromboplastin time, fibrinogen, d-dimer, plasminogen, antithrombin, platelet, protein C and S, lupus anticoagulant, and cardiolipin antibodies; VDRL was within the reference range. CONCLUSION: The authors suggest abnormal thromboembolism as a presumed mechanism of the pathogenesis of MMD in this patient.

Pituitary abscess in a pregnant woman.

Pituitary abscess is a rare and potentially lethal condition. Pituitary abscess in a pregnant woman has not been previously described. A 38-year-old pregnant woman (34 weeks gestation) with a pituitary mass complained of a progressive headache and sudden visual impairment. She was afebrile and had no inflammatory symptoms on admission. On MRI, the preoperative diagnosis was pituitary adenoma with sphenoid sinusitis. She underwent an uncomplicated transsphenoidal procedure for removal of the pituitary mass. The next day, labor commenced and a healthy preterm baby was delivered. Pathologic examination of the intrasellar mass showed polymorphonuclear cells, debris and no tumor cells. The sellar contents were cultured and Streptococcus viridans was grown. To our knowledge this is the first case of pituitary abscess reported during pregnancy. Although the patient was pregnant, the transsphenoidal approach was safe for the mother and the fetus. Surgical drainage and antibiotic therapy are required for the definitive treatment of this condition.

A simple prediction score system for malignant brain edema progression in large hemispheric infarction.

Malignant brain edema (MBE) due to hemispheric infarction can result in brain herniation, poor outcomes, and death; outcome may be improved if certain interventions, such as decompressive craniectomy, are performed early. We sought to generate a prediction score to easily identify those patients at high risk for MBE. 121 patients with large hemispheric infarction (LHI) (2011 to 2014) were included. Patients were divided into two groups: those who developed MBE and those who did not. Independent predictors of MBE were identified by logistic regression and a score was developed. Four factors were independently associated with MBE: baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.048), Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (p = 0.007), collateral score (CS) (p<0.001) and revascularization failure (p = 0.013). Points were assigned for each factor as follows: NIHSS ≤ 8 (= 0), 9-17 (= 1), ≥ 18 (= 2); ASPECTS≤ 7 (= 1), >8 (= 0); CS<2 (= 1), ≥2 (= 0); revascularization failure (= 1),success (= 0). The MBE Score (MBES) represents the sum of these individual points. Of 26 patients with a MBES of 0 to 1, none developed MBE. All patients with a MBES of 6 developed MBE. Both MBE development and functional outcomes were strongly associated with the MBES (p = 0.007 and 0.002, respectively). The MBE score is a simple reliable tool for the prediction of MBE.

Bypass surgery versus medical treatment for symptomatic moyamoya disease in adults.

OBJECTIVE In this study the authors evaluated whether extracranial-intracranial bypass surgery can prevent stroke occurrence and decrease mortality in adult patients with symptomatic moyamoya disease (MMD). METHODS The medical records of 249 consecutive adult patients with symptomatic MMD that was confirmed by digital subtraction angiography between 2002 and 2011 at 8 institutions were retrospectively reviewed. The study outcomes of stroke recurrence as a primary event and death during the 6-year follow-up and perioperative complications within 30 days as secondary events were compared between the bypass and medical treatment groups. RESULTS The bypass group comprised 158 (63.5%) patients, and the medical treatment group comprised 91 (36.5%) patients. For 249 adult patients with MMD, bypass surgery showed an HR of 0.48 (95% CI 0.27-0.86, p = 0.014) for stroke recurrence calculated by Cox regression analysis. However, for the 153 patients with ischemic MMD, the HR of bypass surgery for stroke recurrence was 1.07 (95% CI 0.43-2.66, p = 0.887). For the 96 patients with hemorrhagic MMD, the multivariable adjusted HR of bypass surgery for stroke recurrence was 0.18 (95% CI 0.06-0.49, p = 0.001). For the treatment modality, indirect bypass and direct bypass (or combined bypass) did not show any significant difference for stroke recurrence, perioperative stroke, or mortality (log rank; p = 0.524, p = 0.828, and p = 0.616, respectively). CONCLUSIONS During the treatment of symptomatic MMD in adults, bypass surgery reduces stroke recurrence for the hemorrhagic type, but it does not do so for the ischemic type. The best choice of bypass methods in adult patients with MMD is uncertain. In adult ischemic MMD, a prospective randomized study to evaluate the effectiveness and safety of bypass surgery to prevent recurrent stroke is necessary.

Inductin of neuron-derived orphan receptor-1 in the dentate gyrus of the hippocampal formation following transient global ischemia in the rat.

Neuron-derived orphan receptor (NOR-1) is a member of the thyroid/steroid receptor superfamily that was originally identified in forebrain neuronal cells undergoing apoptosis. In addition to apoptotic stimuli, activation of several signal transduction pathways including direct neuronal depolarization regulates the expression of NOR-1. In this study we tested whether the expression of NOR-1 is changed following transient ischemic injury in the adult rat brain. NOR-1 mRNA increased rapidly in the dentate gyrus of the hippocampal formation and piriform cortex 3 h after transient global ischemia and returned to basal level at 6 h. On the other hand, oxygen-glucose deprivation of cultured cerebral cortical neurons did not alter the expression of NOR-1. These results suggest that expression of NOR-1 is differentially regulated in different brain regions in response to globally applied brain ischemia, but that hypoxia is not sufficient to induce its expression.

Induction of CITED2 expression in the rat hippocampus following transient global ischemia.

CITED2 is implicated in the modulating the activity of HIF-1 which is a major transcription factor involved in ischemia-related gene expression. Following transient forebrain ischemia, we found that CITED2 was induced in a subset of brain regions including dentate gyrus of the hippocampal formation and piriform cortex. Because CITED2 was not induced in cultured neurons exposed to oxygen-glucose deprivation, we concluded that hypoxia is not sufficient to trigger its induction.

Diagnostic method for differentiating external hydrocephalus from simple subdural hygroma.

OBJECT: The various terms used to describe subdural fluid collection--"external hydrocephalus", "subdural hygroma", "subdural effusion", "benign subdural collection", and "extraventricular obstructive hydrocephalus"-reflect the confusion surrounding the diagnoses of these diseases. Differentiating external hydrocephalus from simple subdural hygroma may be difficult, but the former appears to be a distinct clinical entity separate from the latter. In this report, the authors present a diagnostic method for differentiating external hydrocephalus from simple subdural hygroma, based on their clinical experience in treating subdural fluid collection after mild head trauma. METHODS: Twenty patients with subdural fluid collection after mild head trauma were included in this study. Ventricle size was measured using a modified frontal horn index (mFHI); that is, the largest width of the frontal horns divided by the bicortical distance in the same plane, instead of the inner table distance. Bur hole trephination was performed on the appearance of a subdural fluid collection thicker than 15 mm on computed tomography (CT), persistent (longer than 4 weeks) or increasing in size, and accompanied by neurological symptoms (confusion or memory impairment). During the procedure, subdural pressure was measured using a manometer before opening the dura mater. Subdural pressure varied among the patients, ranging from 3 to 27.5 cm H2O. Four patients with a subdural pressure greater than 15 cm H2O had hydrocephalus after surgery (p < 0.05). Hydrocephalus developed in a pediatric patient (2 years old) with a subdural pressure of 12 cm H2O. All of the patients in whom hydrocephalus developed after bur hole trephination had had enlarged ventricles (mFHI > 33%) on preoperative CT scans. CONCLUSIONS: Monitoring subdural pressure may be a valuable tool for differentiating subdural hygroma from external hydrocephalus in patients with mild head trauma. Additionally, the mFHI reflects the nature of the subdural collection more accurately than the standard frontal horn index.

Coexisting intracranial meningeal melanocytoma, dermoid tumor, and Dandy-Walker cyst in a patient with neurocutaneous melanosis. Case report.

Neurocutaneous melanosis (NCM) associated with Dandy-Walker malformation is a very rare congenital neurodysplasia with the same origin. Primary intracranial melanocytic and dermoid tumors are also benign congenital lesions that usually arise from the leptomeninges and are formed by the inclusion of cutaneous ectoderm at the time of neural tube closure. The authors describe a patient with coexisting intracranial meningeal melanocytoma, NCM with Dandy-Walker malformation, and intraventricular dermoid tumor.

Combined direct anastomosis and encephaloduroarteriogaleosynangiosis using inverted superficial temporal artery-galeal flap and superficial temporal artery-galeal pedicle in adult moyamoya disease.

BACKGROUND: We evaluated the efficacy of combined STA-MCA anastomosis and EDAGS using inverted STAGF and STAGP for the treatment of adult MMD. METHODS: This study included 8 patients with nonhemorrhagic MMD. There were 6 women and 2 men who were between 23 and 62 years old (mean = 37.8 years) in the sample. The combined surgery was performed on 12 sides in the 8 patients. The surgical results were assessed for clinical outcome, angiographic revascularization, and hemodynamic change on HMPAO brain SPECT. The follow-up period ranged from 6 to 62 months (mean = 27 months). RESULTS: Clinical symptoms and signs were improved or stabilized, and the extent of revascularization evident on external carotid angiograms was excellent in all 8 patients. The CBF on HMPAO SPECT also improved in all 12 sides that were operated on with the combined surgery, except for the preexisting infarcted area, on the basal as well as Diamox stimulation studies. One patient had a transient speech disturbance after surgery, and another patient had delayed wound healing. CONCLUSIONS: The combined STA-MCA anastomosis and EDAGS using inverted STAGF/P seems to be one of the most effective surgical modalities for the treatment of nonhemorrhagic MMD in adults.

Parenchymal neurocutaneous melanosis in association with intraventricular dermoid and Dandy-Walker variant: a case report.

Neurocutaneous melanosis (NCM) is a rare congenital disease that is characterized by the presence of large or multiple congenital melanocytic nevi and melanotic lesions of the central nervous system. We report here on the CT and MR imaging findings of an unusual case of NCM that was associated with intraventricular dermoid and Dandy-Walker malformation.

Association of apolipoprotein E gene polymorphism with small-vessel lesions and stroke type in moyamoya disease: a preliminary study.

OBJECT The present study was conducted to investigate whether microbleeds or microinfarcts are associated with apolipoprotein E (APOE) gene polymorphisms in patients with moyamoya disease (MMD), and if so, whetherAPOE gene polymorphisms are also associated with stroke type in patients with MMD. METHODS This cross-sectional, multicenter study included 86 consecutive patients with MMD who underwent T2*-weighted gradient echo or susceptibility-weighted MR imaging and 83 healthy control volunteers. Baseline clinical and radiological characteristics were recorded at diagnosis, and inter- and intragroup differences in the APOE genotypes were assessed. Multivariate binary logistic regression models were used to determine the association factors for small-vessel lesions (SVLs) and hemorrhagic presentation in patients with MMD. RESULTS There was no difference in APOE gene polymorphism and the incidence of SVLs between patients with MMD and healthy controls (p > 0.05). In the MMD group, 7 (8.1%) patients had microbleeds and 32 (37.2%) patients had microinfarcts. Microbleeds were more frequently identified in patients with hemorrhagic-type than in nonhemorrhagictype MMD (p = 0.003). APOE genotypes differed according to the presence of microbleeds (p = 0.024). APOE ε2 or ε4 carriers also experienced microbleeds more frequently than APOE ε3/ε3 carriers (p = 0.013). In the multivariate regression analysis in patients with MMD, microbleeds were significantly related to APOE ε2 or ε4 carrier status (OR 7.86; 95% CI1.20-51.62; p = 0.032) and cerebral aneurysm (OR 17.31; 95% CI 2.09-143.57; p = 0.008). Microinfarcts were independently associated with hypertension (OR 3.01; 95% CI 1.05-7.86; p = 0.007). Hemorrhagic presentation was markedly associated with microbleeds (OR 10.63; 95% CI 1.11-102.0; p = 0.041). CONCLUSIONS These preliminary results did not show a difference in APOE gene polymorphisms between patients with MMD and healthy persons. However, they imply that APOE gene polymorphisms may play certain roles in the presence of microbleeds but not microinfarcts in patients with MMD. A further confirmatory study is necessary to elucidate the effect of APOE gene polymorphisms and SVLs on the future incidence of stroke in patients with MMD.