Association of Age-Related Spontaneous Internal Jugular Vein Reflux with Cognitive Impairment and Incident Dementia.

BACKGROUND: It remains unclear whether changes in the venous circulation contribute to cognitive decline. OBJECTIVE: This study aimed to clarify whether the spontaneous jugular vein reflux (JVR) is associated with cognitive impairment and incident dementia. METHODS: Patients with any evidence of cerebral vessel disease on magnetic resonance imaging (MRI) were consecutively enrolled between October 2015 to July 2019. We employed carotid duplex sonography to measure the internal jugular vein (IJV). The subjects were classified into two groups based on the degree of JVR on either side: none, mild (JVR(-) group) and moderate, severe (JVR (+) group) JVR. They underwent both the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Japanese (MoCA-J) global tests. Their cognitive status was prospectively assessed until March 2023. RESULTS: 302 patients with an MMSE score ≥24 underwent duplex sonography of the IJV. Among them, 91 had spontaneous JVR on either side. Both MMSE and MoCA-J were significantly lower in patients with JVR (+) group than in the JVR (-) group. After the adjustment for risk factors and MRI findings, intergroup differences in MoCA-J remained significant. Among the cognitive subdomains, median executive function and memory scores were significantly lower in the JVR (+) group than in the JVR (-) group. During the median 5.2-year follow-up, 11 patients with incident dementia were diagnosed. Patients with severe JVR were significantly more likely to be diagnosed with dementia (log-rank test, p = 0.031). CONCLUSIONS: Spontaneous IJV reflux especially severe JVR, was associated with global cognitive function, and potentially with incident dementia.

Prevalence of Microembolic Signals in Embolic Stroke of Undetermined Source and Other Subtypes of Ischemic Stroke.

Background and Purpose- Embolic stroke of undetermined source (ESUS) has been proposed to cause thromboembolic infarction from unknown but potential embolic sources. However, an embolus remains undetected in ESUS. The goal of this study was to characterize the prevalence and risk factors of microembolic signals (MESs) in ESUS. Methods- We examined 108 patients with acute ischemic stroke in the internal carotid artery territory or transient ischemic attack within 14 days of symptom onset and who were admitted to our hospital between April 2017 and March 2019. MESs were monitored in the middle cerebral artery on transcranial Doppler for 60 minutes. We examined the prevalence and number of MES in ESUS and other stroke subtypes, such as cardioembolism, large artery atherosclerosis, cerebral small vessel disease, and transient ischemic attack. The present study was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000031913). Results- MESs were detected in 33 (31%) of 108 patients. ESUS showed the highest proportion (12/24 [50%]), followed by large artery atherosclerosis (8/20 [40%]), cardioembolism (6/18 [33%]), transient ischemic attack (4/24 [17%]), and cerebral small vessel disease (3/21 [14%]). Univariate analysis showed that higher systolic blood pressure, body mass index, hemoglobin A1c, and ESUS were significantly associated with MES. In multiple logistic regression analysis, ESUS remained significantly associated with MES after adjustment for described covariates from univariate analysis (odds ratio, 2.86 [95% CI, 1.01-8.08]). Conclusions- This study demonstrated significant association of ESUS with MES, supporting the embolic nature of this stroke subtype. Registration- URL: https://upload.umin.ac.jp. Unique identifier: UMIN000031913.

Differences in Endothelial Function between Ischemic Stroke Subtypes.

BACKGROUND: Endothelial dysfunction plays a key role in the development of ischemic stroke. However, the relationship between endothelial function and stroke subtypes has not been thoroughly examined. METHODS: We measured the percentage of brachial flow-mediated vasodilatation (%FMD) in 62 patients with chronic stroke and 13 age- and sex-matched control patients. Patients with stroke included those classified into large artery atherosclerosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment classification. RESULTS: %FMD was significantly lower in the patients with any of LAA, CE, and SVO than in the control patients. %FMD was also significantly lower in men than in women as well as in patients with than without hypertension or diabetes mellitus. After adjustment for confounding factors, the patients with LAA and CE but not SVO had lower %FMD compared to the controls. CONCLUSIONS: Our results suggest that endothelial function in conduit artery was impaired in patients with LAA and CE regardless with or without concomitant vascular risk factors.

Ulcerated carotid plaques with ultrasonic echolucency are causatively associated with thromboembolic cerebrovascular events.

The presence of ulcerated carotid plaques is a risk factor for ischemic stroke, which is associated with thromboembolism. We evaluated the relationship between ulcerated carotid plaques and cerebrovascular events in patients with acute ischemic stroke or transient ischemic attack. We extracted 48 consecutive patients with ulcerated carotid plaques from a cohort of 1111 patients with acute ischemic stroke or transient ischemic attack. All patients were evaluated by carotid ultrasonography and diffusion-weighted magnetic resonance imaging. We defined thromboembolic events by excluding potential cardiac sources of embolism, stroke in posterior circulation, contralateral lesions, and single and small (<1.5 cm) subcortical lesions, and we considered the remaining patients with cortical lesions or multiple or large subcortical lesions as having experienced a thromboembolic cerebrovascular event. We compared ultrasonographic findings in the patients with and those without a thromboembolic cerebrovascular event. A relationship with thromboembolic events was suspected in 10 patients (21%) with ulcerated carotid plaques. The proportion of smokers was significantly higher in the group of patients with a thromboembolic event (90% vs 53%; P = .03). Logistic regression demonstrated a significant association between thromboembolic events and the presence of echolucent ulcerated plaques (odds ratio, 9.34, 95% confidence interval, 1.65-53.0), even though maximum intima-media thickness and other variables of ulcerated plaques (eg, depth of ulcers, thickness of the plaque, or the degree of stenosis) did not differ significantly between the 2 groups. Our findings indicate that although cerebrovascular events are closely associated with echolucent ulcerated carotid plaques, the prevalence of thromboembolism was not very high (∼20%) in our cohort of Japanese patients with ulcerated carotid plaques.

Renin-angiotensin system blockade safely reduces blood pressure in patients with minor ischemic stroke during the acute phase.

The ACCESS (Acute Candesartan Cilexetil Therapy in Stroke Survivors) study found that administration of candesartan in the acute phase of stroke confers a long-term benefit in patients who have sustained acute ischemic stroke. This treatment did not significantly reduce blood pressure (BP) during the acute phase, however. We assessed the short-term safety of reducing BP with renin-angiotensin system blockade in hypertensive patients who sustained acute ischemic stroke. Our randomized study compared the effects of 14 days of oral candesartan (4 mg/day), perindopril (4 mg/day), or conventional therapy (topical nitrate only when systolic BP (SBP) was ≥220 mm Hg or diastolic BP (DBP) was ≥120 mm Hg) administered to hypertensive patients within 72 hours of the onset of minor ischemic stroke. We assessed neurologic symptoms using the National Institutes of Health Stroke Scale and the modified Rankin Scale within 72 hours of stroke onset before and after drug therapy. A total of 40 patients completed the protocol. Therapy with candesartan and perindopril reduced SBP/DBP values by 23/11 mm Hg (SBP, P<.01; DBP, P=.07) and 14/0 mm Hg (SBP, P=.07), respectively, compared with conventional treatment. Neurologic symptoms worsened in 2 patients who received perindopril, which has no statistical significance, despite the BP reduction in patients given candesartan or perindopril. Our findings indicate that low doses of candesartan or perindopril safely reduce SBP in hypertensive patients with acute ischemic stroke.

Smell identification in Japanese Parkinson's disease patients: using the odor stick identification test for Japanese subjects.

OBJECTIVE: The purpose of the present study was to clarify the olfactory functions of Japanese patients with idiopathic Parkinson's disease (IPD) using the odor stick identification test for Japanese (OSIT-J). METHODS: Fifty-four non-demented IPD patients (33 men and 21 women), ranging in age from 43 to 81 years (69.7+/-8.1 years) and 50 age- and gender-matched healthy controls who reported having no olfactory complaints were enrolled. OSIT-J consisted of 12 odorants familiar to Japanese subjects. Each subject sniffed each odor that was applied to paraffin paper. Next the subject chose 1 of 6 answers: 4 pictures associated with the odors labeled with their names, one of which was correct, and 2 other ones ("unknown" and "not detected"). RESULTS: The number of correct answers was significantly lower in the IPD group (4.4+/-2.7) than in the normal group (8.3+/-2.2) (p<0.0001). Even in IPD patients who could smell normal strength odors in subjective symptom, the number of correct answers decreased. The number of correct answers was not correlated with motor function, disease duration, or medication. CONCLUSION: The present study demonstrated that the smell identification ability of Japanese IPD patients was impaired based on the OSIT-J.

[QuantiFERON: an early diagnostic tool for cerebral tuberculosis].

Two cases (a 33-year-old woman and a 34-year-old man) were diagnosed as having cerebral tuberculosis. Case 1 was tuberculoma with miliary tuberculosis complicating cranial nerve palsies, and case 2 was tuberculous meningitis. Early diagnosis was difficult, because smear and PCR were negative. Culture was finally positive after several weeks. QuantiFERON were positive prior to the culture results in both cases. This reaction suggested tuberculous infection. QuantiFERON is useful for diagnosing cerebral tuberculosis at an early stage.

Clinical characteristics of stroke patients with antiphospholipid antibodies.

BACKGROUND: Antiphospholipid syndrome is important as a cause of ischemic stroke, although clinical characteristics of the syndrome are not well documented. METHODS: We analyzed differences in clinical characteristics between 40 antiphospholipid-antibody (aPL)-positive and 40 aPL-negative stroke patients. RESULTS: Stroke patients with aPL were significantly younger and were more likely to be women in comparison with stroke patients without aPL. Valvular heart disease, neurological complications and hematological disorders were more frequent in the aPL-positive group. The mean value of thrombin-antithrombin III complex was significantly lower in the aPL-positive group. Cerebral infarctions in the carotid system were less and large-artery lesions more frequent in the aPL-positive patients. CONCLUSIONS: Stroke patients with aPL have clinical characteristics distinct from stroke patients without aPL.

[Myelopathy in patients with antiphospholipid antibodies: clinical features, pathogenesis, and review of literature].

We report 5 patients with anti-cardiolipin IgM-positive myelopathy. The lengths of spinal lesions were over two vertebral segments in 4 patients. Four cases showed subacute onset, and 2 out of these 4 cases had inflammatory changes in cerebrospinal fluid (CSF), and all of their symptoms improved. However, in one patient who showed an acute onset and normal findings of CSF, neurological symptoms did not improve. Three patients fulfilled the diagnostic criteria of primary antiphospholipid antibody syndrome. As for the pathophysiology of myelitis associated with antiphospholipid antibodies (aPL), it is suggested that vascular thrombosis affecting the blood cord barrier promotes an inflammatory changes. The heterogeneous CFS findings seem to reflect the difference in the intensity of inflammation. Both vascular thrombosis and inflammatory process should be considered as pathogenesis of these patients. Alone or combination therapy of steroids and anticoagulants might be effective in patients of myelopathy associated with APS.

[A young patient with endometrioid adenocarcinoma who suffered Trousseau's syndrome associated with vasculitis].

A 27-year-old woman was admitted to our hospital because of headache, fever and right neck pain. Neurological examination revealed mild meningeal signs, and hyper-reflexia in all extremities. In the laboratory tests, white-cell count was 13,000/mm3, rheumatoid factor(RF) and C-reactive protein(CRP) were positive. The cerebro-spinal fluid showed pleocytosis (56/mm3, neutorophils and lymphocytes were 26 and 28, respectively). Thus, she was diagnosed as aseptic meningitis. A few days later, she had weakness and dysesthesia of the right face and the left extremities. Pulse therapy with intravenous methylprednisolone was started. A magnetic resonance imaging (MRI) of the brain showed a hemorrhagic infarction in the right parietal lobe. In hemostatic markers, thrombin-antithrombin III complex(TAT; 106 ng/dl), D-dimer 1234 ng/dl, prothrombin fragment 1 + 2(F1 + 2; 2.36 nmol/L), beta-thromboglobulin (beta TG; 4,300 ng/dl) and platelet factor 4 (PF-4; 1,770 ng/dl) were extremely elevated. On duplex ultrasonography, a low echo lucent plaque was observed at the right internal carotid artery and the mean blood flow velocity in the right carotid artery was decreased. She was placed on oral prednisolone and warfarin for suspected stroke due to hypercoagulability associated with vasculitis. Afterwards, she discharged from our hospital. Two months later, she was readmitted to our hospital because of irregular menses and vaginal bleeding. Endometrial uterus biopsy was conducted, which revealed a grade I endometrioid adenocarcinoma. She was under total uterectomy without tumor recurrence. After the radical operation, white-cell count, RF, CRP, TAT, D-dimer, F1 + 2, and beta TG were normalized, and the mean flow velocity of the right common carotid artery was increased. Thereafter, she did not experience stroke recurrence. Therefore, we speculated that she had stroke due to hypercoagulability in association with malignancy, that is Trousseau's syndrome. We also assumed that aseptic meningitis, brainstem encephalitis associated with vasculitis in this patient are other clinical variants of paraneoplastic syndrome through immunological mechanisms associated with malignancy. We emphasize that patients with Trousseau's syndrome can be associated with other paraneoplastic manifestations such as vasculitis as seen in this patient.

[An ambulatory respirometer (Hotmate) as a tool for screening of sleep apnea syndrome].

The gold standard diagnostic method for sleep apnea syndrome(SAS) is overnight polysomnography(PSG), but is costly in terms of time and money. We studied the usefulness of a 24-hour ambulatory respirometer equipped with oximeter(Hotmate) for screening of SAS. Seventy-six cases of suspected SAS were enrolled(68 males and 8 females, mean age 51). The correlation between data from Hotmate and PSG was evaluated in 24 cases who underwent both of the tests for the final diagnosis of SAS. There was a good correlation between the two parameters of the data obtained by Hotmate(H) (H-apnea index(AI) vs H-desaturation index(DI)). Among 24 cases who underwent both Hotmate and PSG, there was a good correlation between the data from PSG and Hotmate(PSG-AI vs H-AI: r = 0.80, p < 0.001). Both sensitivity and specificity were highest when screening criteria of H-DI > 15 was utilized(sensitivity = 91.7%, specificity = 66.7%). Our findings suggest that the respiromonitor with oximeter is useful for the screening the patients with SAS.