PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety.

Background: Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT. Methods: We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles. Results: Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time. Conclusion: Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.

Moderate-Intensity Rosuvastatin Plus Ezetimibe Versus High-Intensity Rosuvastatin for Target Low-Density Lipoprotein Cholesterol Goal Achievement in Patients With Recent Ischemic Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. METHODS: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. RESULTS: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352-2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. CONCLUSION: Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

Sex differences in the progression of cerebral microbleeds in patients with concomitant cerebral small vessel disease.

Background and purpose: Sex differences in cerebral microbleeds (CMBs) are not well-known. We aimed to assess the impact of sex on the progression of CMBs. Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Out of 256 subjects, 189 participants with a follow-up brain scan were included in the analysis. The linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between men and women. Results: A total of 65 men and 124 women were analyzed. There were no significant differences in the prevalence (70.8 vs. 71.8%; P = 1.000) and the median [interquartile range (IQR)] number of total CMBs [1 (0-7) vs. 2 (0-7); P = 0.810] at baseline between men and women. The median (IQR) increase over 2 years in the number of CMBs was statistically higher in women than in men [1 (0-2) vs. 0 (0-1), P = 0.026]. The multivariate linear mixed-effects model showed that women had a significantly greater increase in the number of total, deep, and lobar CMBs compared to men after adjusting for age and the baseline number of CMBs [estimated log-transformed mean of difference between women and men: 0.040 (P = 0.028) for total CMBs, 0.037 (P = 0.047) for deep CMBs, and 0.047 (P = 0.009) for lobar CMBs]. Conclusion: The progression of CMB over 2 years was significantly greater in women than in men.

A case report and experience of endovascular treatment for a patient with hemophilia who had a hyperacute ischemic stroke.

No previous study has reported endovascular treatment (EVT) in a patient with hemophilia who had an acute ischemic stroke (AIS). Herein, we report the case of a patient with hemophilia A who presented with hyperacute stroke due to a near occlusion of the proximal internal carotid artery (ICA). A 54-year-old man was admitted to our emergency department with a sudden onset of left-sided weakness that occurred 4 hours prior to admission. He had been diagnosed with congenital hemophilia A during his childhood. Although brain computed tomography revealed no evidence of hemorrhage, we did not consider intravenous thrombolysis because of his bleeding-prone condition. Diffusion-weighted imaging revealed a restricted diffusion in the right anterior and middle cerebral artery territories. Magnetic resonance angiography revealed that the right proximal ICA was nearly occluded and had a residual stump. Digital subtraction angiography revealed a near occlusion of the right proximal ICA with a thread-like lumen. Balloon angioplasty was performed in the proximal ICA, and distal flow was restored, but residual stenosis was observed. Stepwise revascularization by carotid endarterectomy (CEA) was planned instead of immediate carotid stenting. He underwent CEA with preoperative and postoperative coverage of factor VIII and recovered without any bleeding complication.

Sleep Apnea and Early Neurological Deterioration in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Evidence of an association between sleep apnea (SA) and early neurological deterioration (END) in acute phase ischemic stroke is scant. We investigated the prevalence of SA and the impact of SA severity on END in acute ischemic stroke (AIS) patients. METHODS: We prospectively enrolled consecutive AIS patients admitted to our stroke unit within 72 hours of symptom onset. SA severity was assessed with ApneaLink-a validated portable respiratory monitor. SA was defined as an apnea-hypopnea index (AHI) of greater than or equal to 5 per hour. END was defined as an incremental increase in the National Institutes of Health Stroke Scale (NIHSS) score by greater than or equal to 1 point in motor power, or greater than or equal to 2 points in the total score within the first week after admission. RESULTS: Of the 305 patients studied, 254 (83.3%) patients had SA (AHI ≥ 5 per hour), and of these, 114 (37.4%) had mild SA (AHI 5-14 per hour), 59 (19.3%) had moderate SA (AHI 15-29 per hour), and 81 (26.6%) had severe SA (AHI ≥ 30 per hour). Thirty-six (11.8%) patients experienced END: 2 of the 51 (3.9%) patients without SA and 34 of the 254 (14.4%) patients with SA. Multivariable regression analysis showed AHI independently predicted END (odds ratio 1.024; 95% confidence interval 1.006 to 1.042; P = .008). CONCLUSIONS: SA is common in the acute phase of ischemic stroke, and SA severity is associated with the risk of END.

Blood pressure variability and hemorrhagic transformation in patients with successful recanalization after endovascular recanalization therapy: A retrospective observational study.

OBJECTIVE: Although blood pressure (BP) variability has been regarded as a risk factor for hemorrhagic transformation (HTF) after intravenous thrombolysis, its effect on HTF after endovascular recanalization therapy (ERT) remains to be elucidated. We aimed to study the relationship between BP variability and symptomatic intracerebral hemorrhage (sICH) after successful recanalization with ERT. METHODS: A total of 211 patients with acute ischemic stroke and successful recanalization (thrombolysis in cerebral infarction 2b or 3) after ERT were included between January 2013 and May 2017. The BP data following ERT was obtained over the first 24 hours using parameters including mean, maximum, minimum, difference between maximum and minimum, standard deviation, coefficient of variation, successive variations, and time rate (TR) of BP variation for systolic BP (SBP) and diastolic BP. sICH was defined as parenchymal hemorrhage type 2 with neurological deterioration of 4 points of more on the National Institute of Health Stroke Scale. RESULTS: Among the included patients, 20 (9.5%) developed sICH after successful ERT. The parameters linked with BP fluctuation over time were significantly related to sICH. After adjusting for confounders, the TR of SBP (per 0.1 mmHg/min increase) variation was independently associated with sICH (odds ratio = 1.71, 95% confidence interval = 1.013-2.886). INTERPRETATION: Time-related BP variability in the first 24 hours following successful ERT was more correlated with sICH than other absolute BP levels. This suggests that maintaining a stable BP may be an important factor in preventing sICH after successful ERT. Ann Neurol 2019;85:574-581.

Yield of Screening Tests for Systemic Vasculitis in Young Adults with Ischemic Stroke.

Systemic vasculitis, which can involve the brain, may be one of the causes of stroke in young adults; therefore, a test panel for systemic vasculitis is considered for some young stroke patients. However, little is known about this test's yield as a screening test in young adults with ischemic stroke. We evaluated the yield of a panel for systemic vasculitis as a screening test in young patients with ischemic stroke. Consecutive patients aged 18-45 years with ischemic stroke between January 2010 and December 2017 were included. They all underwent screening tests for systemic vasculitis including rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, anticardiolipin antibody, lupus anticoagulant, anti-DNA antibody, and anti-Ro/SSA and La/SSB antibodies. Among 3,593 consecutive patients with acute ischemic stroke during the study period, 198 (5.5%) were aged 18-45 years. Only 4 patients (2.0%) were diagnosed with systemic vasculitis; 2 had systemic lupus erythematosus, 1 had Sjogren's syndrome, and 1 had Churg-Strauss syndrome. Vasculitis panel screening in every young ischemic stroke patient is not of high yield unless a vasculitic process is highly suspected based on other systemic symptoms or signs of vasculitis. Screening should be targeted toward persons with clinical suspicion.

Is antiplatelet treatment effective at attenuating the progression of white matter hyperintensities?

OBJECTIVE: We performed this study to assess the effect of an antiplatelet agent on the progression of white matter hyperintensities (WMH). METHODS: From August 2003 to May 2005, we consecutively enrolled patients who underwent brain magnetic resonance imaging (MRI) for health check-up purposes and showed no significant findings other than WMH of any degree. Patients were divided into two groups based on whether or not they received antiplatelet therapy. All patients had a follow-up brain MRI after 5 years and WMH volume change was measured using imaging analysis software. To minimize selection bias potentially arising from antiplatelet treatment assignment, analyses were inverse probability weighted. RESULTS: Among the 93 patients who met the inclusion criteria, 54 patients (58.1%) were grouped as the antiplatelet group (AG), and the remaining 39 patients (41.9%) as the non-antiplatelet group (NAG). After inverse propensity weighting, all baseline characteristics were similar between the two groups, and antiplatelet treatment did not show any significant effect on the total WMH volume change (p = 0.957). CONCLUSION: Antiplatelet medication may not alter the progression of WMH.

A Case of Turner Syndrome with Multiple Embolic Infarcts.

Only a few cases of Turner syndrome (TS) with ischemic stroke have been reported. Various arteriopathies of the cerebral arteries, including fibromuscular dysplasia, congenital hypoplasia, moyamoya syndrome, and premature atherosclerosis have been assumed to be the cause of ischemic stroke in TS. There has been no case report of a TS patient presenting with an embolic stroke pattern without any cerebral arteriopathy. A 28-year-old woman with TS was referred to our hospital because of abnormal brain magnetic resonance imaging (MRI) findings. She underwent brain MRI at the referring hospital because she experienced sudden-onset diffuse headache. Diffusion-weighted imaging revealed multiple acute embolic infarcts in different vascular territories. Intracranial and extracranial arterial disease was not detected on cerebral magnetic resonance angiography and carotid sonography. Embolic source workups, including transthoracic and transesophageal echocardiography, Holter monitoring, and transcranial Doppler shunt study, were all negative. Hypercoagulability and vasculitis panels were also negative. Our patient was diagnosed with cryptogenic embolic stroke. This is the first report of a TS patient with an embolic stroke pattern. Our case shows that ischemic stroke in TS could be due to embolism as well as the various cerebral arteriopathies documented in previous reports.

The clinico-oncologic outcomes of elderly patients with glioblastoma after surgical resection followed by concomitant chemo-radiotherapy.

BACKGROUND: There have been controversies in the treatment of elderly patients with glioblastoma. We introduce the outcome of the treatment of elderly patients with glioblastoma comparing with younger patients. METHODS: The author's hospital database was used to identify patients with histologically confirmed glioblastoma after surgery between January 2006 and December 2013. Forty-eight patients (control group) were under age 65 and 16 patients (elderly group) were aged 65 years or over at the time of surgery. RESULTS: The median age of the elderly group was 71 years and control group was 50 years. Mean number of medical comorbidities was 1.8 in the elderly group vs. 0.5 in the control group. The median progression free survival (PFS) was 5.6 months and the median overall survival (OS) was 19.9 months in all patients. The elderly group had a median PFS of 4.2 months vs. 8 months for the control group (log-rank test, p=0.762). Median OS was 8.2 months in the elderly group vs. 20.9 months in the control group (log-rank test, p=0.457). Major complications occurred in 5 cases (7.8%) for all patients. The ratio of completion of concomitant chemo-radiotherapy (CCRT) was 81.3% and was the same between the two groups. In multivariable analysis, extent of resection (p=0.034) and completion of CCRT (p=0.023) were statistically significant, independent prognostic factors only for PFS in all patients by Cox proportional hazards model. Age was not an independent prognostic factor. As for OS, there was no significant factor. CONCLUSION: Surgical resection and CCRT were well tolerated in elderly patients with glioblastoma, and maximal safe resection followed by timely CCRT could improve clinic-oncologic outcomes.

Endovascular management of great vessel injury following lumbar microdiscectomy.

Great vessel injury is a rare but well-known complication of lumbar disc surgery, which may result in acute or fatal outcomes of delayed diagnosis. Thus, early detection and proper management is vital. The authors report a case of retroperitoneal hemorrhage with arteriovenous fistula and pseudoaneurysm after lumbar microdiscectomy. The patient was successfully managed by endovascular intervention using a stent graft. Endovascular repair is a minimally invasive and efficient treatment modality with considerably low morbidity and mortality.

Familial hemiplegic migraine with prolonged coma and cerebellar atrophy: CACNA1A T666M mutation in a Korean family.

We report the first Korean patient with familial hemiplegic migraine type 1, with clinical and multimodal imaging findings. A 43-yr-old man was admitted for right hemianopia and aphasia, followed by coma. MRI showed only cerebellar atrophy. CT angiography showed mild vasodilation of intracranial blood vessels and increased vascularity in the left hemisphere and perfusion-weighted imaging showed elevated cerebral blood flow. Gene analysis of the patient and his mother led to the identification of a heterozygous point mutation (1997C→T, T666M) in exon 16 of the CACNA1A gene. Familial hemiplegic migraine should be considered in patients with episodic neurological dysfunction with cerebellar atrophy.

Measuring sleep quality after adenotonsillectomy in pediatric sleep apnea.

OBJECTIVES/HYPOTHESIS: The aim of this study was to demonstrate postoperative changes in sleep quality in children with obstructive sleep apnea (OSA), using both conventional sleep staging and electrocardiogram-based cardiopulmonary coupling (CPC) analysis. The hypothesis is that being electroencephalography (EEG)-independent, CPC may detect changes in sleep quality that traditional sleep architecture analysis cannot. STUDY DESIGN: Retrospective outcome research. METHODS: We included 37 children (aged 6.89 ± 2.76 years, 28 male) with OSA who underwent adenotonsillectomy, and analyzed standard polysomnography and CPC parameters from a full-night study before and after adenotonsillectomy. High-frequency coupling (HFC) and low-frequency coupling (LFC) were used as indices of stable and unstable sleep, respectively. RESULTS: Adenotonsillectomy led to a significant change in CPC parameters (HFC, 50.3 ± 16.1% to 56.1 ± 14.7%, P = .03; LFC, 35.1 ± 14.5% to 27.3 ± 13.0%, P = .003), which was paralleled by improvements in the apnea-hypopnea (12.7 ± 13.7 to 1.0 ± 0.8, P < .001) and arousal index (20.8 ± 11.5 to 9.9 ± 3.9, P < .001). Polysomnographic sleep stage parameters other than the arousal index did not reflect postoperative resolution of OSA. CONCLUSIONS: In pediatric OSA, postoperative improvement of sleep quality is more readily discernible by CPC analysis than EEG-based sleep staging. The CPC analysis may have potential advantages in the assessment of sleep quality in pediatric populations.

Association between irritable bowel syndrome and restless legs syndrome in the general population.

This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005-2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL(-1) P = 0.004) and higher highly sensitive C-reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL(-1), P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74-3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.

Decreased cortical complexity in methamphetamine abusers.

This study aimed to investigate if methamphetamine (MA) abusers exhibit alterations in complexity of the electroencephalogram (EEG) and to determine if these possible alterations are associated with their abuse patterns. EEGs were recorded from 48 former MA-dependent males and 20 age- and sex-matched healthy subjects. Approximate Entropy (ApEn), an information-theoretical measure of irregularity, of the EEGs was estimated to quantify the degree of cortical complexity. The ApEn values in MA abusers were significantly lower than those of healthy subjects in most of the cortical regions, indicating decreased cortical complexity of MA abusers, which may be associated with impairment in specialization and integration of cortical activities owing to MA abuse. Moreover, ApEn values exhibited significant correlations with the clinical factors including abuse patterns, symptoms of psychoses, and their concurrent drinking and smoking habits. These findings provide insights into abnormal information processing in MA abusers and suggest that ApEn of EEG recordings may be used as a potential supplementary tool for quantitative diagnosis of MA abuse. This is the first investigation to assess the "severity-dependent dynamical complexity" of EEG patterns in former MA abusers and their associations with the subjects' abuse patterns and other clinical measures.

Age-dependent association between cigarette smoking on white matter hyperintensities.

Previous reports have shown that cigarette smoking is associated with white matter hyperintensities (WMHs). However, it remains unclear whether this is true for all ages. We investigated the association between cigarette smoking, WMHs, and age. We retrospectively reviewed charts from 595 patients, who presented as outpatients from January 2007 to March 2010. Grading of periventricular WMHs (PVWMHs) and the scores of deep WMHs (DWMHs) was determined based on criteria established by the Rotterdam Scan Study. We compared the degree of WMHs between smokers and non-smokers, and those younger than the age of 65 years versus those above. In younger age group, smokers had higher grades of PVWMHs and more microbleeds than non-smokers. In the older age group, total burden of DWMHs was much greater in smokers than nonsmokers. Multivariate regression analysis showed that cigarette smoking was an independent risk factor for PVWMHs in the younger age group and for DWMHs in the older age group. The location of WMHs in association with smoking seems to differ among age groups. Age should be considered when interpreting the effects of smoking on the brain.

Dynamic temporal change of cerebral microbleeds: long-term follow-up MRI study.

BACKGROUND: Cerebral microbleeds (MBs) are understood as an important radiologic marker of intracerebral hemorrhage. We sought to investigate the temporal changes of MBs and clinical factors associated with the changes using long-term follow-up MRI. METHODS/PRINCIPAL FINDINGS: From October 2002 to July 2006, we prospectively enrolled patients with stroke or transient ischemic attack, and followed-up their brain MRIs with an interval >12 mo. We compared demographic factors, vascular risk factors, laboratory findings, and radiologic factors according to the presence or changes of MBs. A total of 224 patients successfully completed the follow-up examinations (mean, 27 months). Newly developed MBs were noted in 10 patients (6.8%) among those without MBs at baseline (n = 148), and in those with MBs at baseline (n = 76), the MB count had decreased in 11 patients (14.5%), and increased in 41 patients (53.9%). The estimated annual rate of change of MB numbers was 0.80 lesions per year in all patients, a value which became greater in those patients who exhibited MBs at baseline (MBs≥5, 5.43 lesions per year). Strokes due to small vessel occlusion and intracerebral hemorrhage, as well as white matter lesions were independently associated with an increased MB count, whereas the highest quartile of low-density lipoprotein (LDL) cholesterol was associated with a decreased MB count. CONCLUSION: During the follow-up period, most of MBs showed dynamic temporal change. Symptomatic or asymptomatic small vessel diseases appear to act as risk factors while in contrast, a high level of LDL cholesterol may act as a protective factor against MB increase.

Small deep white matter lesions are associated with right-to-left shunts in migraineurs.

The right-to-left shunts (RLS) and white matter lesions (WMLs) are frequently observed in migraineurs and in patients with ischemic stroke. Previous studies have reported that the burden of WMLs did not increase with the intracardiac right-to-left shunt (RLS) in migraineurs. However, some types of WMLs are known to be associated with RLS in patients with stroke and dementia. The aim of the study was to demonstrate the difference in the size and location of WMLs, according to the existence of RLS in patients with headache. From the prospective headache registry, a total of 425 subjects (age, 30.8 ± 5.1 years; 303 women; 242 migraineurs; 183 patients with tension-type headache (TTH)) were retrospectively reviewed and evaluated for RLS and WMLs using M-mode power transcranial Doppler sonography (mTCD) and brain magnetic resonance imaging scans. We scored WMLs, according to the Rotterdam Scan Study, and assessed the association between RLS presence and the location and size of WMLs. The number of small deep WMLs (dWMLs) and the prevalence of RLS, defined as microembolic signals (MES) ≥ 11, were higher in patients with migraine (small dWMLs, 6.23 vs. 4.05; RLS, 36.8% vs. 10.9%), compared to patients with TTH. There was no significant difference in the sum of periventricular WML grades or the total volume of dWMLs between TTH and migraine patients. Among the migraineurs, the patients with RLS more frequently had small dWMLs, aura, and heart disease compared to those without RLS. In addition, RLS were also independent predictors for the presence of small dWMLs from the multivariate binary regression analysis (p < 0.01; OR = 3.24; 95%CI 1.56-6.72). Small dWMLs are associated with RLS in young migraineurs. These results imply that paradoxical embolism may cause the small WMLs in some migraineurs.

Role of cortical dysplasia in epileptogenesis following prolonged febrile seizure.

PURPOSE: Hippocampal sclerosis, characterized by prominent neuronal loss and reactive gliosis, is the most common pathology in human temporal lobe epilepsy (TLE). Although prolonged febrile convulsion (FC) is a risk factor of TLE, it is not clear whether FC provokes hippocampal sclerosis and subsequent TLE. Given that underlying brain lesions, such as cortical dysplasia (CD), in the immature brain predispose patients to FC, CD may link FC and TLE. However, the role of CD in epileptogenesis after FC is also unclear. Here, we investigated whether inborn CD increases the risk of later epilepsy induced by prolonged FC using a rat model. METHODS: Experimental CD was induced by in utero exposure of methylazoxymethanol (MAM). Rat pups from MAM-treated or control rats were then subjected to prolonged FC. We examined morphologic changes in the hippocampi with respect to neuronal loss, reactive gliosis, and synaptogenesis, and evaluated spontaneous recurrent seizures (SRS) by long-term video-EEG (electroencephalography). RESULTS: The MAM+FC group had a significantly lower hippocampal neuronal density in the CA1 and dentate hilus than other control groups. A robust increase in glial cells and synaptic reorganization was also detected in the MAM+FC groups. Furthermore, later SRS occurred in all rats in the MAM+FC group and in 50% and 25% of the rats in the FC-only and MAM-only group, respectively. The frequency and total duration of SRS was highest in the MAM+FC group. DISCUSSION: Our results suggest that preexisting CD in the immature brain augments the proepileptogenic effects of prolonged FC, leading to TLE.