Imaging follow-up strategy after endovascular treatment of Intracranial aneurysms: A literature review and guideline recommendations.

OBJECTIVE: Endovascular coil embolization is the primary treatment modality for intracranial aneurysms. However, its long-term durability remains of concern, with a considerable proportion of cases requiring aneurysm reopening and retreatment. Therefore, establishing optimal follow-up imaging protocols is necessary to ensure a durable occlusion. This study aimed to develop guidelines for follow-up imaging strategies after endovascular treatment of intracranial aneurysms. METHODS: A committee comprising members of the Korean Neuroendovascular Society and other relevant societies was formed. A literature review and analyses of the major published guidelines were conducted to gather evidence. A panel of 40 experts convened to achieve a consensus on the recommendations using the modified Delphi method. RESULTS: The panel members reached the following consensus: 1. Schedule the initial follow-up imaging within 3-6 months of treatment. 2. Noninvasive imaging modalities, such as three-dimensional time-of-flight magnetic resonance angiography (MRA) or contrast-enhanced MRA, are alternatives to digital subtraction angiography (DSA) during the first follow-up. 3. Schedule mid-term follow-up imaging at 1, 2, 4, and 6 years after the initial treatment. 4. If noninvasive imaging reveals unstable changes in the treated aneurysms, DSA should be considered. 5. Consider late-term follow-up imaging every 3-5 years for lifelong monitoring of patients with unstable changes or at high risk of recurrence. CONCLUSIONS: The guidelines aim to provide physicians with the information to make informed decisions and provide patients with high-quality care. However, owing to a lack of specific recommendations and scientific data, these guidelines are based on expert consensus and should be considered in conjunction with individual patient characteristics and circumstances.

Safety and Efficacy of Flow Diverter Therapy for Unruptured Intracranial Aneurysm Compared to Traditional Endovascular Strategy : A Multi-Center, Randomized, Open-Label Trial.

OBJECTIVE: Endovascular treatment of large, wide-necked intracranial aneurysms by coil embolization is often complicated by low rates of complete occlusion and high rates of recurrence. A flow diverter device has been shown to be safe and effective for the treatment of not only large and giant unruptured aneurysms, but small and medium aneurysms. However, in Korea, its use has only recently been approved for aneurysms <10 mm. This study aims to compare the safety and efficacy of flow diversion and coil embolization for the treatment of unruptured aneurysms ≥7 mm. METHODS: The participants will include patients aged between 19 and 75 years to be treated for unruptured cerebral aneurysms ≥7 mm for the first time or for recurrent aneurysms after initial endovascular coil embolization. Participants assigned to a flow diversion cohort will be treated using any of the following devices : Pipeline Flex Embolization Device with Shield Technology (Medtronic, Minneapolis, MN, USA), Surpass Evolve (Stryker Neurovascular, Fremont, CA, USA), and FRED or FRED Jr. (MicroVention, Tustin, CA, USA). Participants assigned to a coil embolization cohort will undergo traditional endovascular coiling. The primary endpoint will be complete occlusion confirmed by cerebral angiography at 12 months after treatment. Secondary safety outcomes will evaluate periprocedural and post-procedural complications for up to 12 months. RESULTS: The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. CONCLUSION: This article describes the aim and design of a multi-center, randomized, open-label trial to compare the safety and efficacy of flow diversion versus traditional endovascular treatment for unruptured cerebral aneurysms ≥7 mm.

Optimal Duration of Dual Antiplatelet Therapy after Stent- Assisted Coil Embolization of Unruptured Intracranial Aneurysms : A Prospective Randomized Multicenter Trial.

OBJECTIVE: Stent-assisted coil embolization (SAC) has been increasingly used to treat various types of intracranial aneurysms. Delayed thromboembolic complications are major concerns regarding this procedure, so dual antiplatelet therapy with aspirin and clopidogrel is needed. However, clinicians vary the duration of dual antiplatelet therapy after SAC, and no randomized study has been performed. This study aims to compare the safety and efficacy of long-term (12 months) dual antiplatelet therapy and shortterm dual antiplatelet therapy (6 months) after SAC for patients with unruptured intracranial aneurysms (UIAs). METHODS: This is a prospective, randomized and multicenter trial to investigate the optimal duration of dual antiplatelet therapy after SAC in patients with UIAs. Subjects will receive dual antiplatelet therapy for 6 months (short-term group) or 12 months (longterm group) after SAC. The primary endpoint is the assessment of thromboembolic complications between 1 and 18 months after SAC. We will enroll 528 subjects (264 subjects in each group) and perform 1 : 1 randomization. This study will involve 14 topperforming, high-volume Korean institutions specializing in coil embolization. RESULTS: The trial will begin enrollment in 2022, and clinical data will be available after enrollment and follow-up. CONCLUSION: This article describes that the aim of this prospective randomized multicenter trial is to compare the effect of short-term (6 months) and long-term (12 months) dual antiplatelet therapy on UIAs in patients undergoing SAC, and to find the optimal duration.

Central Sarcopenia, Frailty and Comorbidity as Predictor of Surgical Outcome in Elderly Patients with Degenerative Spine Disease.

OBJECTIVE: People are living longer and the elderly population continues to increase. The incidence of degenerative spinal diseases (DSDs) in the elderly population is quite high. Therefore, we are facing more cases of DSD and offering more surgical solutions in geriatric patients. Understanding the significance and association of frailty and central sarcopenia as risk factors for spinal surgery in elderly patients will be helpful in improving surgical outcomes. We conducted a retrospective cohort analysis of prospectively collected data to assess the impact of preoperative central sarcopenia, frailty, and comorbidity on surgical outcome in elderly patients with DSD. METHODS: We conducted a retrospective analysis of patients who underwent elective spinal surgery performed from January 1, 2019 to September 30, 2020 at our hospital. We included patients aged 65 and over who underwent surgery on the thoracic or lumbar spine and were diagnosed as DSD. Central sarcopenia was measured by the 50th percentile of psoas : L4 vertebral index (PLVI) using the cross-sectional area of the psoas muscle. We used the Korean version of the fatigue, resistance, ambulation, illnesses, and loss of weight (K-FRAIL) scale to measure frailty. Comorbidity was confirmed and scored using the Charlson Comorbidity Index (CCI). As a tool for measuring surgical outcome, we used the Clavien-Dindo (CD) classification for postoperative complications and the length of stay (LOS). RESULTS: This study included 85 patients (35 males and 50 females). The mean age was 74.05±6.47 years. Using the K-FRAIL scale, four patients were scored as robust, 44 patients were pre-frail and 37 patients were frail. The mean PLVI was 0.61±0.19. According to the CD classification, 50 patients were classified as grade 1, 19 as grade 2, and four as grade 4. The mean LOS was 12.35±8.17 days. Multivariate stepwise regression analysis showed that postoperative complication was significantly associated with surgical invasiveness and K-FRAIL scale. LOS was significantly associated with surgical invasiveness and CCI. K-FRAIL scale showed a significant correlation with CCI and PLVI. CONCLUSION: The present study demonstrates that frailty, comorbidity, and surgical invasiveness are important risk factors for postoperative complications and LOS in elderly patients with DSD. Preoperative recognition of these factors may be useful for perioperative optimization, risk stratification, and patient counseling.

Erratum: Correction of Text and Table 1 in the Article "National Trends in the Treatment of Ruptured Cerebral Aneurysms in Korea Using an Age-adjusted Method".

This corrects the article on p. e323 in vol. 35, PMID: 33045768.

National Trends in the Treatment of Ruptured Cerebral Aneurysms in Korea Using an Age-adjusted Method.

BACKGROUND: Two primary treatment methods are used for ruptured cerebral aneurysms, surgical clipping and endovascular coiling. In recent decades, endovascular coiling has shown remarkable progress compared to surgical clipping, along with technological developments. The aim of this study was to investigate the recent trends in treatments for ruptured cerebral aneurysms in Korea. METHODS: The data were obtained from the National Health Insurance database. We evaluated the trends in endovascular coiling and surgical clipping for ruptured aneurysms for the period 2000-2017. We obtained the number of prescriptions with International Classification of Diseases, 9th Revision, clinical modification codes related to nontraumatic subarachnoid hemorrhage and prescription codes S4641/4642 for surgical clipping and M1661/1662 for endovascular coiling. The medical expenses for each prescription were also obtained. The primary outcomes included the cumulative number of patients, patient rates per 100,000 people, and the correlation between patient rates and the percentage of the population in each age group. RESULTS: In the case of surgical clipping, there were no increasing or decreasing trends in the cumulative number of patients when the population/age group was ignored. When examining the trends in patient rates per 100,000 population at each year in male, there was no increasing or decreasing trend in the number of surgical clippings between the age groups, in spite of a decreasing tendency in the number of surgical clipping in male in their 40s and older than 60. In females, the surgical clipping rates tended to decrease only in patients older than 60 years, but there was no tendency to increase or decrease in the other ages. In contrast, the cumulative number of patients who underwent endovascular coiling for ruptured cerebral aneurysms increased year by year regardless of the population/age group. In both male and female, there was no increasing or decreasing trend only in the group aged 40 or younger and there was an increasing tendency in the rest of the age groups. In the trend of medical expenses, both the cost of surgical clipping and endovascular coiling showed increases. Specifically, the medical expense trend in endovascular coiling increased more rapidly than that for surgical clipping. CONCLUSION: There was a significant increase in the proportion of patients with ruptured aneurysms undergoing endovascular coiling between 2010 and 2017, whereas the use of surgical clipping decreased. The endovascular coiling was significantly increased in all age groups and surgical clipping was decreased in all age groups, especially in patients under 50 years of age.

The Influence of Comorbidities on Reoperations Following Primary Surgery of Lumbar Degenerative Diseases : A Nationwide Population-Based Retrospective Cohort Study from 2009-2016.

OBJECTIVE: Spinal degeneration is a progressive disease, worsening over time. Lumbar degenerative disease (LDD) is a major spinal disease in elderly patients. Surgical treatment is considered for medically intractable patients with LDD and reoperation after primary surgery is not uncommon. The surgical outcome is occasionally unpredictable because of comorbidities. In the present study, the relationship between comorbidities and the incidence of reoperation for LDD over time was determined. METHODS: The claims data of the health insurance national database were used to identify a cohort of patients who underwent spinal surgery for LDD in 2009. The patients were followed up until 2016. Medical comorbidity was assessed according to the Charlson comorbidity index (CCI). Cox proportional hazard regression modeling was used to identify significant differences in sex, surgery, age, causative disease, and comorbidity. RESULTS: The study cohort included 78241 patients; 10328 patients (13.2%) underwent reoperation during the observation period. The reoperation rate was statistically higher (p<0.01) in males, patients 55-74 years and 65-74 years of age, and patients with decompression or discectomy. Significant association was found between increasing reoperation rate and CCI score (p<0.01). Based on multivariate analysis of comorbidities, the significantly higher reoperation rates were observed in patients with peripheral vascular disease, pulmonary lung disease, peptic ulcer, diabetes, and diabetes complications (p<0.01). CONCLUSION: The study results indicate the reoperation rate for LDD is associated with patient comorbidities. The comorbidities identified in this study could be helpful in future LDD studies.

The Efficacy of P2Y12 Reactive Unit to Predict the Periprocedural Thromboembolic and Hemorrhagic Complications According to Clopidogrel Responsiveness and Safety of Modification of Dual Antiplatelet Therapy : A Meta-Analysis.

The efficacy of P2Y12 reaction unit (PRU) of VerifyNow still remains as a controversial issue in neurointervention. So we investigated the usefulness of PRU of VerifyNow to predict the peri-procedural thromboembolic events (TE) and hemorrhagic events (HE). And we evaluated the safety of modified dual antiplatelet therapy (DAPT) or triple antiplatelet therapy (TAPT) for clopidogrel hyporesponders. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus on August 19 2018. Data was collected the 1) incidence of TE between clopidogrel responder and clopidogrel hypo-responder, 2) incidence of HE between clopidogrel hyper-responder and clopidogrel responder and hypo-responder, and 3) incidence of TE and HE between modified DAPT or TAPT and standard DAPT in clopidogrel hypo-responder. High cut-off value of PRU was defined as PRU >40% or <220. Fifteen studies were enrolled. Clopidogrel responder showed lower incidence of TE than hypo-responder (risk ratio [RR], 0.32; 95% confidence interval [CI], 0.17-0.61; p<0.001). With the high cut-off value of PRU, clopidogrel responder showed more lower incidence of TE than hypo-responder (RR, 0.11; 95% CI, 0.02-0.45; p=0.002). The incidence of periprocedural HE have higher on clopidogrel hyper-responder than clopidogrel responder and hypo-responder (RR, 4.26; 95% CI, 1.10-16.44; p=0.04; I2=66%). The incidence of periprocedural TE after changing regimen of DAPT for clopidogrel hypo-responder have a tendency to reduce, but there was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). The incidence of periprocedural HE after changing regimen of DAPT for clopidogrel hypo-responder was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). PRU is a useful tool as a predictor of peri-procedural TE or HE on neurointervention. PRU has a threshold effect of cut-off value to predict the peri-procedural TE. Modified DAPT or TAPT to prevent TE in clopidogrel hypo-responders could not reduce the incidence of TE. We should investigate the further research about modification of regiment on neurointervention.

Disappearance of Arachnoid Cyst after Burrhole Trephination: Case Series.

We report 3 cases of arachnoid cysts (ACs) that completely disappeared after burr hole drainage, without cyst fenestration into the subarachnoid space or cystoperitoneal shunt. The first patient was a 21-year-old female with an AC of the right cerebral convexity, found incidentally. After endoscopic AC fenestration was performed, the patient complained of persistent headache. Two-month postoperative brain imaging revealed reaccumulated AC and associated multi-stage subdural hematoma. Burr hole drainage was performed to resolve the chronic subdural hematoma (CSDH). Three months later, brain computed tomography showed that the CSDH and the AC had disappeared. The second patient was an 11-year-old male who had a history of trauma 1 month prior to presentation at the clinic. Brain magnetic resonance imaging revealed an AC in the left sylvian fissure with CSDH. We performed burr hole drainage to treat the CSDH first. Subsequently, the AC as well as the CSDH disappeared. The third case was an AC of the right parietal convexity, found incidentally. Only burr hole drainage was performed, following which, the AC disappeared. This case series shows that an AC can disappear naturally after rupture into the subdural space by trauma or the burr hole procedure.

Current Training Status of Neurosurgical Residents in South Korea: A Nationwide Multicenter Survey.

BACKGROUND: In South Korea, special legislation was introduced in December 2016 to limit residents' training time to a maximum of 80 hours per week. The aim of this study was to survey the current training system and environment of neurosurgical residents and to find ways to improve the quality of neurosurgical training. METHODS: The questionnaire survey included 373 neurosurgical residents at 66 training hospitals nationwide, who were members of the Korean Neurosurgical Society. The survey method included a questionnaire link through a text message and was carried out anonymously. The survey was conducted for 7 days and targeted a total of 106 residents (28.4%). RESULTS: Most respondents selected "excessive training time" as a reason for dissatisfaction with the training environment (n = 61, 57.5%), followed by "limited number of opportunities for surgery" (n = 50, 47.2%), and "little experience for research" (n = 42, 39.6%). Respondents still believe that they have to work excessively longer, even after 80 hours of training per week. CONCLUSIONS: The major reason that neurosurgical residents are dissatisfied with the current training system and environment is the excessive time spent on it. These survey results are expected to be used as the basis for improvement of the residents' training system and work environment in South Korea.

Usefulness of Middle Meningeal Embolization to Prevent Recurrent Spontaneous Chronic Subdural Hemorrhage.

Spontaneous chronic subdural hematoma (SDH) is a rare condition that could develop in association with hematologic disease. A 66-year-old male developed a chronic SDH as an initial manifestation of chronic myelomonocytic leukemia (CMML). He experienced recurrent chronic subdural hemorrhage and newly developed intracerebral hemorrhage. Considering the scheduled long-term chemotherapy, bilateral middle meningeal artery (MMA) embolization was performed to prevent recurrence of subdural hemorrhage. Although pancytopenia occurred during the 7 months' follow-up period, residual chronic subdural hemorrhage was absorbed without recurrence. To our best knowledge, this is the first report of CMML with spontaneous chronic SDH. MMA embolization is potentially a useful and safe treatment option in the challenging clinical situations with underlying pathologies.

Korean Clinical Practice Guidelines for Aneurysmal Subarachnoid Hemorrhage.

Despite advancements in treating ruptured cerebral aneurysms, an aneurysmal subarachnoid hemorrhage (aSAH) is still a grave cerebrovascular disease associated with a high rate of morbidity and mortality. Based on the literature published to date, worldwide academic and governmental committees have developed clinical practice guidelines (CPGs) to propose standards for disease management in order to achieve the best treatment outcomes for aSAHs. In 2013, the Korean Society of Cerebrovascular Surgeons issued a Korean version of the CPGs for aSAHs. The group researched all articles and major foreign CPGs published in English until December 2015 using several search engines. Based on these articles, levels of evidence and grades of recommendations were determined by our society as well as by other related Quality Control Committees from neurointervention, neurology and rehabilitation medicine. The Korean version of the CPGs for aSAHs includes risk factors, diagnosis, initial management, medical and surgical management to prevent rebleeding, management of delayed cerebral ischemia and vasospasm, treatment of hydrocephalus, treatment of medical complications and early rehabilitation. The CPGs are not the absolute standard but are the present reference as the evidence is still incomplete, each environment of clinical practice is different, and there is a high probability of variation in the current recommendations. The CPGs will be useful in the fields of clinical practice and research.

Geographic Analysis of Neurosurgery Workforce in Korea.

OBJECTIVE: In respect of the health and safety of the public, universal access to health care is an issue of the greatest importance. The geographic distribution of doctors is one of the important factors contributing to access to health care. The aim of this study is to assess the imbalances in the geographic distribution of neurosurgeons across Korea. METHODS: Population data was obtained from the National Statistical Office. We classified geographic groups into 7 metropolitan cities, 78 non-metropolitan cities, and 77 rural areas. The number of doctors and neurosurgeons per 100000 populations in each county unit was calculated using the total number of doctors and neurosurgeons at the country level from 2009 to 2015. The density levels of neurosurgeon and doctor were calculated and depicted in maps. RESULTS: Between 2009 and 2015, the number of neurosurgeons increased from 2002 to 2557, and the ratio of neurosurgeons per 100000 populations increased from 4.02 to 4.96. The number of neurosurgeons per 100000 populations was highest in metropolitan cities and lowest in rural areas from 2009 to 2015. A comparison of the geographic distribution of neurosurgeons in 2009 and 2015 showed an increase in the regional gap. The neurosurgeon density was affected by country unit characteristics (p=0.000). CONCLUSION: Distribution of neurosurgeons throughout Korea is uneven. Neurosurgeons are being increasingly concentrated in a limited number of metropolitan cities. This phenomenon will need to be accounted when planning for a supply of neurosurgeons, allocation of resources and manpower, and the provision of regional neurosurgical services.

Numbers of Stroke Patients and Stroke Subtypes According to Highest and Lowest Daily Temperatures in Seoul.

BACKGROUND AND PURPOSE: There is conflicting evidence for whether or not the incidence of stroke is influenced by the daily temperature. The association between daily temperature and incidence of stroke is largely unknown in Korea. This study attempted to evaluate whether the maximum or minimum daily temperature is associated with increased numbers of strokes and stroke subtypes among Seoul residents. METHODS: We obtained the maximum and minimum daily temperatures in Seoul from the Korean Meteorological Administration between January 2005 and December 2014. Consecutive patients with acute stroke were registered who visited the emergency room or outpatient clinic in Soonchunhyang University Hospital, Seoul. The residential addresses of cases were restricted to within a 2-kilometer radius of this hospital. The stroke events were prospectively recorded with onset time, and were classified by subtypes. The categories of daily temperature were divided by 10℃ from the mean temperature. The mean daily number of strokes was calculated during the study period. One-way analysis of variance and Duncan's post-hoc test were applied to compare the number of strokes among the temperature groups. RESULTS: In total, 2,313 acute strokes were identified during the period: 1,643 ischemic strokes and 670 hemorrhagic strokes. The number of cases was significantly higher when the maximum daily temperature was >32℃ or ≤3℃ (p=0.048) or the minimum daily temperature was ≤-11.0℃ (p=0.020). The lowest maximum daily temperature was associated with increased instances of intracerebral hemorrhage (p=0.029) and small-vessel occlusion (p=0.013), while the highest maximum daily temperature was associated with an increased instance of large-artery atherosclerosis (p=0.045). CONCLUSIONS: The daily temperature had measurable and different associations with the number of strokes and strokes subtypes in Seoul, Korea.

Update of the Korean Clinical Practice Guidelines for Endovascular Recanalization Therapy in Patients with Acute Ischemic Stroke.

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.

Y-configuration Stent-assisted Coil Embolization for Wide-necked Intracranial Bifurcation Aneurysms.

OBJECTIVE: The objective of this study was to determine the efficiency and safety of Y configuration stent-assisted coiling with double-closed stents for wide-necked intracranial aneurysms located at arterial bifurcations thorough analysis of a multicenter case series. MATERIALS AND METHODS: A retrospective chart review was done on 10 patients who underwent endovascular treatment of wide-necked intracranial aneurysms with Y-configuration stent-assisted coil embolization in three centers from August 2011 to March 2014. The degree of aneurysmal occlusion was assessed using the Raymond scale. Clinical outcomes were assessed before operation, at discharge, and at the last follow-up visit using the Glasgow outcome scale. RESULTS: The 10 patients included 6 females and 4 males with a mean age of 58.6 years. Indications for treatment included 6 unruptured intracranial aneurysms and 4 ruptured intracranial aneurysms. Five aneurysms were located at the basilar artery bifurcation, four aneurysms were located in an anterior communicating artery, and one aneurysm was in the pericallosal artery. The mean size of the 10 aneurysms was 9.7 mm. All aneurysms had a dome-to-neck ratio of < 1.5 (mean, 0.89). Immediate complications included one thromboembolic event out of the 10 cases. Immediate posttreatment angiograms showed complete occlusion in 1 aneurysm and residual necks in 9 aneurysms. Follow-up results showed 8 complete occlusions and 2 residual necks. No delayed complications were observed during the follow-up period (mean: 20 months). CONCLUSION: Y configuration using double-closed cell stents is feasible and safe in selected patients. This method is an acceptable option for managing complex wide-necked bifurcations.

Unexpected Severe Cerebral Edema after Cranioplasty : Case Report and Literature Review.

This report details a case of unexpected, severe post-operative cerebral edema following cranioplasty. We discuss the possible pathological mechanisms of this complication. A 50-year-old female was admitted to our department with sudden onset of stuporous consciousness. A brain computed tomography (CT) revealed a subarachnoid hemorrhage with intracranial hemorrhage and subdural hematoma. Emergency decompressive craniectomy and aneurysmal neck clipping were performed. Following recovery, the decision was made to proceed with an autologous cranioplasty. The cranioplasty procedure was free of complications. An epidural drain was placed and connected to a suction system during skin closure to avoid epidural blood accumulation. However, following the procedure, the patient had a seizure in the recovery room. An emergency brain CT scan revealed widespread cerebral edema, and the catheter drain was clamped. The increased intracranial pressure and cerebral edema were controlled with osmotic diuretics, corticosteroids, and antiepileptic drugs. The edema slowly subsided, but new low-density areas were noted in the brain on follow-up CT 1 week later. We speculated that placing the epidural drain on active suction may have caused an acute decrease in intracranial pressure and subsequent rapid expansion of the brain, which impaired autoregulation and led to reperfusion injury.

Clinical significance of cerebral microbleeds locations in CADASIL with R544C NOTCH3 mutation.

BACKGROUND AND PURPOSE: Although cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common single-gene disorder of cerebral small blood vessels caused by NOTCH3 mutations, little has been described about the variation in the clinical findings between its underlying types of mutations. In particular, the presence of cerebral microbleeds (CMBs) has been an increasingly recognized magnetic resonance imaging finding in CADASIL, but their clinical significance is not clear. The purpose of this study is to assess whether CMBs are associated with symptomatic stroke in the CADASIL patients with R544C mutation and to compare the cerebral distribution of CMBs between CADASIL patients with and without symptomatic stroke. METHODS: This is a cohort study of patients who were diagnosed with genotype-confirmed R544C-mutation CADASIL. Primary neurologic symptoms were recorded. Symptomatic strokes were defined as transient ischemic attack, ischemic strokes and hemorrhagic strokes. CMBs were defined as focal areas of round signal loss on T2*-weighted gradient echo planar images with a diameter of less than 10 mm. The locations of CMBs were divided into lobar, basal ganglia, thalamus, brain stem and cerebellum. Multiple logistic regressions were performed to identify the epidemiologic or vascular risk factors associated with symptomatic stroke in patients with CADASIL. RESULTS: Among total of 51 subjects in this cohort, CMBs were present in 20 of 32 patients (64.5%) in the symptomatic stroke-group and in 8 of 19 patients (42.1%) in the non-stroke group (p = 0.16). CMBs were observed more frequently in the basal ganglia (p<0.001) and the cerebellum (p<0.018) in the symptomatic stoke group compared to the non-stroke group. The mean number of CMBs was significantly higher in the symptomatic stroke group (15.4±18.0 lesions per patients with CMBs) versus those without symptomatic stroke (3.3±3.0 lesions per patients with CMBs) (p = 0.003). Hypertension was an independent risk factor for symptomatic stroke in CADASIL (p = 0.014). It was independently associated with CMBs locations as basal ganglia (p = 0.016), thalamus (p = 0.010), brainstem (p = 0.044), and cerebellum (p = 0.049). However, It was not independently associated with CMBs on lobar lesion (p = 0.152). CONCLUSIONS: In this study hypertension was an independent predictor of CMBs presence in specific brain locations, as well as symptomatic stroke in the CADASIL patients. The distribution and burden of CMBs might be a clinically useful marker for the risk of symptomatic stroke. However, further prospective studies on the relationship between CMBs distribution and symptomatic stroke are required in order to support these preliminary findings.