Background We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast-enhanced ultrasound ( CEUS ). Methods and Results We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative CEUS and magnetic resonance plaque imaging. We distinguished high-signal-intensity plaques ( HIP s) and non- HIP s based on magnetization-prepared rapid acquisition with gradient echo images. We graded them according to the CEUS contrast effect and compared the CEUS images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as HIP s (43 symptomatic) and 11 were classified as non- HIP s (5 symptomatic). Although the magnetization-prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms ( P=0.07), concomitant use of magnetization-prepared rapid acquisition with gradient echo and CEUS findings did show a significant correlation ( P<0.0001). CEUS showed that all 5 symptomatic non- HIP s had a high-contrast effect. These 5 plaques were histopathologically confirmed as vulnerable, with extensive neovascularization but only a small amount of intraplaque hemorrhage. Conclusions Complementary use of magnetic resonance imaging and CEUS to detect intraplaque hemorrhage and neovascularization in plaques can be useful for evaluating plaque vulnerability, consistent with the destabilization process associated with neovessel formation and subsequent intraplaque hemorrhage.
Introduction: Contrast-enhanced ultrasound (CEUS) using new contrast agents which offer a stable contrast effect in vivo is a noninvasive modality to detect vulnerability of carotid plaque, ulceration and neovascularization. A recent study showed the superiority for the detection of small ulcers using CEUS to color-Doppler ultrasound (CDUS), which used computed tomographic angiography (CTA) as the reference technique. Hypothesis: We assumed CEUS enables us to detect disruption of carotid plaques that could not be detected by CDUS and CTA. We aimed to investigate the diagnostic accuracy for detecting the disruption of the carotid plaques comparing with histopathological findings. Methods: From July 2010 to July 2015, we enrolled 68 internal carotid stenosis (ICS) patients undergoing carotid endarterectomy (CEA) and preoperatively examined CEUS using Perflubutane (Sonazoid), CDUS and CTA. We compared the findings of the plaque disruptions detected by these three modalities with the histopathological findings of ulceration and present/recent plaque rupture. Results: Of 68 subjects (age 72±6.6years old, 66 men), 44 (64%) had symptomatic ICS. Pathologically, ulceration and present/recent plaque rupture were found in 58 cases (85.3%). The diagnostic accuracy for detecting the disruption of carotid plaque by CEUS was significantly superior to other modalities (Table 1). CEUS could find disrupted carotid plaque more accurately than CTA. Conclusions: The assessment of the disruption of the plaques using CEUS was well correlated with pathological findings of plaque rupture, which may help us to evaluate the plaque vulnerability in vivo real time.
Mahjong is one of the most popular Chinese tile games played in Japan. Mahjong-related seizures (MRS) are rare praxis-induced seizures. We identified three patients with MRS from February 2000 to February 2021. All cases were men, with a middle-age onset, generalized convulsive seizures, and lack of non-provoked, myoclonic, and absence seizures. All patients had no or non-specific neuroimaging or electroencephalogram abnormalities. They did not have features linked to idiopathic generalized epilepsy. All patients were seizure-free after behavioral adjustments, although one patient required anti-seizure medication and avoided long duration games. These changes may help other patients with MRS continue playing Mahjong.
Fingolimod has shown considerable efficacy by preventing relapse and disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). Most patients do not show increased relapses after discontinuing fingolimod treatment, but recently a patient with RRMS who relapsed after fingolimod withdrawal was reported. In addition, a patient with anti-aquaporin 4 (AQP) antibodies initially diagnosed with MS was shown to have extensive brain lesions (EBL) after fingolimod treatment.1 We report a patient with recurrent myelitis that relapsed several days after fingolimod initiation, who developed EBL after fingolimod withdrawal. A 53-year-old woman suffered right leg weakness and urinary retention (right Brown–Séquard syndrome at the Th10 level) in July 2006. Cerebrospinal fluid (CSF) analysis revealed a protein level of 82 mg/dL, a white blood cell count of 31/μL (26% polymorphonuclear cells, 74% mononuclear cells), a normal immunoglobulin (Ig) G index (0.55) and no oligoclonal IgG bands as per the isoelectric focusing method. Brain magnetic resonance imaging (MRI) showed no lesions. By December 2007, the patient lost her ability to walk. Spinal cord MRI showed a centrally-located T2 lesion of 2.5-vertebral segment length at the Th2-4 level with an enhancing lesion of 1.5-vertebral segment length of the right spinal cord. The patient regained her walking ability after intravenous corticosteroid pulse therapy (ICPT). In February 2008, the patient was enrolled into a Japanese trial of fingolimod (Fig. 1a),2 and her Expanded Disability Status Scale (EDSS) score was 1.5. A total of 5 days after starting fingolimod therapy (1.25 mg/day), she developed left leg weakness. Neurological examination revealed bilateral lower limb weakness (left dominant: manual muscle test was graded 3–4/0–2), hypesthesia below the bilateral L1 region (left dominant) and hypalgesia/thermohypesthesia below the right L1 region (EDSS score: 7.0). MRI showed a T2 lesion of 3.5-vertebral segment length (longitudinally extensive spinal cord lesion) at the Th3–6 level with an enhancing lesion of 1.5 vertebral segment length (Fig. 1b). Her symptoms disappeared after ICPT. Considering that relapse can result from low drug concentrations insufficient to suppress disease activity, we continued fingolimod administration. Oral fingolimod was discontinued because the patient showed liver dysfunction after 2 months (Fig. 1a). A total of 4 days after the cessation of fingolimod treatment, she developed fever (38°C) without any other symptoms. Brain MRI showed multiple cloud-like enhancing lesions in the bilateral cerebral white matter (Fig. 1c), and spinal cord MRI showed an enhancing lesion at C6. The brain lesions disappeared after ICPT. A total of 3 weeks after discontinuing therapy, she suddenly showed conduction aphasia and amnestic aphasia. Brain MRI showed EBL involving the left temporal lobe (Fig. 1d). Aphasia gradually improved after ICPT. The patient showed no relapse after oral glucocorticoid therapy (25 mg of predonine started 2 months after withdrawal of fingolimod and tapered slowly). Cell-based assay3 of the stock sera was positive for anti-AQP 4 antibodies in September 2007. Anti-AQP4 antibodies were positive until June 2010 and became negative in January 2011. The EDSS score was 2.5 in March 2013. Although the patient had enrolled into a Japanese trial of fingolimod, she was positive for anti-AQP 4 antibodies with EBL (Fig. 1b), characteristic of neuromyelitis optica (NMO). Although she did not fulfil the diagnostic criteria for NMO or NMO spectrum disorder because there were no contiguous spinal cord MRI lesions extending over three vertebral segments and no history of optic neuritis,4, 5 serum anti-AQP 4 antibodies were present. Therefore, the pathogenesis of her recurrent myelitis might have been related to NMO. The present patient showed relapses early after fingolimod administration and withdrawal. This case suggests that fingolimod administration in patients with NMO or NMO spectrum disorder induces relapse. It is not known whether fingolimod causes worsening of NMO without anti-AQP 4 antibodies; however, its administration should be avoided in patients with NMO or NMO spectrum disorder. Anti-AQP 4 antibodies should be examined before fingolimod initiation, particularly in Asian patients. This study was supported in part by Health and Labor Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour, and Welfare of Japan. None to declare.
Background and Purpose: Lacunar infarction and intracerebral hemorrhage (ICH) are closely related. Although they are classified as different stroke subtypes, both are associated with cerebral small-vessel disease (CSVD). Previous studies showed a positive correlation of CSVD with physiological parameters such as pulse wave velocity (PWV) or with radiographical findings such as cerebral microbleeds (CMB); however, the role of these parameters remains controversial. Therefore, we assessed whether there is a relationship between stroke subtypes and these potential CSVD-related parameters. Methods: In a multicenter, prospective study from 8 hospitals, we enrolled 342 patients with a history of cerebral infarction or ICH who underwent both carotid ultrasound and MRI examination between February 2011 and December 2012. Ischemic stroke subtypes were determined based on the Trial of Org 10172 in Acute Stroke Treatment criteria, and patients with small vessel occlusion (SVO) or large artery atherosclerosis (LAA) were included in this study. We evaluated the PWV, ultrasonographic parameters [max-IMT, plaque score, pulsatility index (PI), and the diameter of common carotid artery (CCA)], and MRI findings [periventricular hyperintensity (PVH) and CMB]. The severity of PVH was determined according to the Fazekas classification. Results: Of 342 patients, 130 (38%) were classified into the LAA group, 64 (19%) into the ICH group, and 148 (43%) into the SVO group. There were no significant differences in the parameters between the SVO and ICH groups; however, the parameters of the SVO or ICH groups were different from those of the LAA group. After adjustment for vascular risk factors, the following parameters in both SVO and ICH groups were significantly different from those in the LAA group: lower plaque score, higher PI of the internal carotid artery (ICA), higher PVH grade, and greater CMB frequency. Conclusion: The SVO and ICH groups showed alterations in imaging parameters reflecting the underlying pathophysiology of CSVD, including lower plaque score, higher PI of ICA, greater CMB frequency, and higher PVH grade, compared with those of the LAA group.
Abstract Background and purpose The management of post‐stroke epilepsy (PSE) should ideally include prevention of both seizure and adverse effects; however, an optimal antiseizure medications (ASM) regimen has yet been established. The purpose of this study is to assess seizure recurrence, retention, and tolerability of older‐generation and newer‐generation ASM for PSE. Methods This prospective multicenter cohort study (PROgnosis of Post‐Stroke Epilepsy [PROPOSE] study) was conducted from November 2014 to September 2019 at eight hospitals. A total of 372 patients admitted and treated with ASM at discharge were recruited. Due to the non‐interventional nature of the study, ASM regimen was not adjusted and followed standard hospital practices. The primary outcome was seizure recurrence in patients receiving older‐generation and newer‐generation ASM. The secondary outcomes were the retention and tolerability of ASM regimens. Results Of the 372 PSE patients with ASM at discharge (median [IQR] age, 73 [64–81] years; 139 women [37.4%]), 36 were treated with older‐generation, 286 with newer‐generation, and 50 with mixed‐generation ASM. In older‐ and newer‐generation ASM groups ( n = 322), 98 patients (30.4%) had recurrent seizures and 91 patients (28.3%) switched ASM regimen during the follow‐up (371 [347–420] days). Seizure recurrence was lower in newer‐generation, compared with the older‐generation, ASM (hazard ratio [HR], 0.42, 95%CI 0.27–0.70; p = .0013). ASM regimen withdrawal and change of dosages were lower in newer‐generation ASM (HR, 0.34, 95% CI 0.21–0.56, p < .0001). Conclusions Newer‐generation ASM possess advantages over older‐generation ASM for secondary prophylaxis of post‐stroke seizures in clinical practice.
