Effect of region-wide use of prehospital stroke triage scale on management of patients with acute stroke.

BACKGROUND: Prehospital stroke triage scales help with the decision to transport patients with suspected stroke to suitable hospitals. OBJECTIVE: To explore the effect of the region-wide use of the Japan Urgent Stroke Triage (JUST) score, which can predict several types of stroke: large vessel occlusion (LVO), intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral infarction other than LVO (CI). METHODS: We implemented the JUST score and conducted a retrospective and prospective multicenter cohort study at 13 centers in Hiroshima from April 1, 2018, to March 31, 2020. We investigated the success rate of the first request to the hospital, on-scene time, and transport time to hospital. We evaluated the door-to-puncture time, puncture-to-reperfusion time, and 90-day outcome among patients with final diagnoses of LVO. RESULTS: The cohort included 5141 patients (2735 before and 2406 after JUST score implementation). Before JUST score implementation, 1269 strokes (46.4%) occurred, including 140 LVO (5.1%), 394 ICH (14.4%), 120 SAH (4.4%), and 615 CI (22.5%). The JUST score was used in 1484 (61.7%) of the 2406 patients after implementation, which included 1267 (52.7%) cases of stroke (186 LVO (7.7%), 405 ICH (16.8%), 109 SAH (4.5%), and 567 CI (23.6%)). Success rate of the first request to the hospital significantly increased after JUST score implementation (76.3% vs 79.7%, p=0.004). JUST score implementation significantly shortened the door-to-puncture time (84 vs 73 min, p=0.03), but the prognosis remained unaltered among patients with acute LVO. CONCLUSIONS: Use of prehospital stroke triage scales improved prehospital management and preparation time of intervention among patients with acute stroke.

[Valproic acid-induced hyperammonemic encephalopathy in a patient receiving valproic acid monotherapy].

A 79-year-old female was diagnosed with epilepsy because she experienced loss of consciousness twice in January and February and then had a seizure in June 2016. She was treated with 800 mg sodium valproate (sustained release). After 3 days, she experienced loss of appetite, and more than 3 days later, disturbance of consciousness. Serum valproic acid (VPA) concentration was 128.3 µg/ml and serum ammonia was 404 µmol/l. Cerebral edema and status epilepticus occurred. Severe neurological dysfunction remained, even after treatment with continuous hemodiafiltration and levocarnitine. VPA is widely used for the treatment of generalized epilepsy. VPA-induced hyperammonemic encephalopathy is a rare but serious adverse event of VPA. Thus, we must pay attention to serum ammonia levels when using VPA, even VPA monotherapy.

Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: A meta-analysis.

OBJECTIVE: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. METHODS: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. RESULTS: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively). CONCLUSIONS: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories.

Prevalences of Peripheral Arterial Disease Diagnosed by Computed Tomography Angiography in Patients with Acute Ischemic Stroke.

BACKGROUND: Few studies have examined the prevalence of peripheral arterial disease (PAD) with the use of computed tomography angiography (CTA) in patients with acute ischemic stroke (AIS), although several reports have examined its prevalence using an ankle brachial index (ABI). We aimed to determine the prevalence of PAD indicated by CTA in patients with AIS and to clarify the prevalence of PAD in each clinical ischemic stroke subtype. METHODS: We included 199 consecutive patients with AIS admitted to our hospital and divided them into PAD and non-PAD groups according to the CTA findings. RESULTS: Of the 199 patients, 40 (20.1%) had PAD; 27 (67.5%) of the PAD patients were asymptomatic. The prevalence of abnormal ABI (≤.9) was 12.2%. Patients with PAD were older (78.3 ± 10.2 versus 71.5 ± 10.9, P <.001) and had a significantly lower ABI value (.89 ± .24 versus 1.15 ± .09, P <.001) and higher prevalence of diabetes mellitus (50.0% versus 31.4%, P = .028), atrial fibrillation (40.0% versus 16.4%, P = .001), coronary artery disease (32.5% versus 8.2%, P <.001), and intracranial arterial stenosis (47.5% versus 28.9%, P = .025) than patients without PAD. The prevalence of cerebral microbleeds was not different between patients with PAD and those without PAD (25.6% versus 25.4%, P = .985). The prevalence of PAD among ischemic stroke subtypes was highest in patients with cardioembolic infarction (40.5%). CONCLUSIONS: Almost one fourth of the AIS patients examined had PAD on CTA. Cardioembolic infarction patients showed the highest prevalence of PAD among the clinical ischemic subtypes, suggesting the coexistence of atheromatous diseases and atrial fibrillation.

Two cases of acute ischemic stroke associated with iron deficiency anemia due to bleeding from uterine fibroids in middle-aged women.

We herein report two cases of acute ischemic stroke associated with iron deficiency anemia (IDA) due to bleeding from uterine fibroids. Anemia is not generally recognized as a risk factor for stroke. The physiological mechanisms that may factor in the development of ischemic stroke in patients with IDA include thrombocytosis, hypercoagulable state, and anemic hypoxia. In our two cases, IDA was considered to be the cause of ischemic stroke because all other known causes of stroke were ruled out. In patients with ischemic stroke due to anemia, early treatment of the anemia is important to prevent stroke recurrence.

The association between hyperintense vessel sign and final ischemic lesion differ in its location.

BACKGROUND: The hyperintense vessel sign (HVS) on fluid-attenuated inversion recovery images can frequently be detected in patients with acute cerebral infarction attributable to large artery stenosis or occlusion. The prognostic values and clinical characteristics of HVS remain to be elucidated. The aim of this study was to evaluate the association of HVS with ischemic lesions and severity of neurologic deficit. METHODS: A total of 96 consecutive acute ischemic stroke patients (54 women, median age 76.5 [range 39-97] years), who had symptomatic severe stenosis or occlusion in the proximal middle cerebral artery that was detected with magnetic resonance angiography within 24 hours of onset, were enrolled. The extent of HVS was graded by a systematic quantitative scoring system (the HVS distribution score) based on Alberta Stroke Program Early Computed Tomographic Score. RESULTS: An HVS was detected in 89 patients (93%) at admission, and the patients who displayed wider HVS distribution scores exhibited more severe neurologic deficits at admission (P<.05). The follow-up magnetic resonance imaging, which was obtained in 79 patients (82%), was performed an average of 13 days. The association between HVS distribution score and final ischemic lesions was strongly observed (n=67, P<.05) but not in the patients with intravenous thrombolysis (n=12, P=.06). CONCLUSIONS: Although the distribution of HVS reflected final ischemic lesion, this association might not apply to the patients with the thrombolysis treatment. The interpretation of HVS distribution score with acute ischemic stroke patients should be discussed dependent on thrombolysis.

Leukocytes may have 2 opposing effects in intravenous rtPA treatment for ischemic stroke.

We hypothesized that leukocytes have 2 opposing effects on patients with ischemic stroke treated with recombinant tissue plasminogen activator (rtPA). Patients with ischemic stroke treated with rtPA were divided into 2 groups using the peripheral leukocyte count: high leukocyte group (HLG) and low leukocyte group (LLG) and were evaluated with the National Institutes of Health stroke scale (NIHSS) during the first 24 hours. We defined significant improvement (SI) as NIHSS improving by more than 50% from the baseline, and deterioration following improvement (DFI) as the achievement of SI within 24 hours but its subsequent loss at 24 hours. Fifty-three patients were enrolled, and the rate of SI within 24 hours was higher in HLG than in LLG (85.2% vs 42.3%, P = .0011). However, the rate of DFI was significantly higher in HLG than in LLG (29.6% vs 7.7%, P = .0413). We found that leukocytes might have not only deleterious but also beneficial effects in intravenous rtPA treatment.

Antiplatelet therapy as a risk factor for microbleeds in intracerebral hemorrhage patients: analysis using specific antiplatelet agents.

BACKGROUND: Although brain microbleed has been reported to be a risk factor for antiplatelet-associated intracerebral hemorrhage, data on the use of specific antiplatelet agents are lacking. In this study, we examined the associations between specific antiplatelets and brain microbleeds in order to help select antiplatelet agents in patients with microbleeds. METHODS: We evaluated 1914 consecutive acute stroke patients, including 412 patients with intracerebral hemorrhage and 1502 patients with ischemic stroke. The associations between the presence of microbleeds and antiplatelet use were evaluated, including specific antiplatelet agents (aspirin, clopidogrel, cilostazol, and ticlopidine). RESULTS: Antiplatelet use was associated with the presence of microbleeds in patients with intracerebral hemorrhage (odds ratio [OR] 2.418; 95% confidence interval [CI] 1.236-4.730; P = .0099), but not in patients with ischemic stroke. The use of a single antiplatelet medication was not associated with the presence of microbleeds. In patients with intracerebral hemorrhage, aspirin (OR 2.160; 95% CI 1.050-4.443; P = .0364) but not clopidogrel, cilostazol, or ticlopidine was associated with microbleeds. In these patients, dividing brain microbleeds into deep microbleeds and lobar microbleeds revealed an association only between antiplatelet use and the presence of deep microbleeds (OR 2.397; 95% CI 1.258-4.567; P = .0079). None of the antiplatelet agents were associated with the presence of deep microbleeds, although aspirin had a trend of association (OR 1.986; 95% CI 1.000-3.946; P = .0501). CONCLUSIONS: Attention to microbleed-positive patients is necessary for the safe use of aspirin in order to avoid antiplatelet-associated hemorrhages, but prospective studies are needed to verify our results.

Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA). METHODS: We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. RESULTS: In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001). CONCLUSIONS: The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.

Serial changes in delayed focal hippocampal lesions in patients with transient global amnesia.

The etiology of transient global amnesia (TGA) is not well understood. MR studies, including studies using diffusion-weighted imaging (DWI), have been used to investigate the pathophysiology of TGA, and focal hippocampal lesions have been detected in some studies. The aim of this study was to investigate serial changes in MR images from the patients with TGA. In seven TGA patients, serial MRI scans (from the same day of the onset to several days after the onset of symptoms) using a 1.5-T MR unit were prospectively evaluated. In four patients, the duration of TGA was over 12 hr. Three of those patients showed small punctate hippocampal hypersensitivity with decreased ADC values on DW images. These lesions were detected in the postacute phase (a time window of 24 - 48 hr after the onset of symptoms). In follow-up studies performed several days after the onset of symptoms, DWI lesions had disappeared in the subacute phase (7-10 days after the TGA episode). The delayed hippocampal lesion on DW images with 1.5-T MRI in patients with TGA appears to be associated with longer duration of symptoms, to persist for several days and to disappear in the chronic phase.

Cytotoxic edema in neuro-Behcet's disease ?

We report a case of a 52-year-old woman with Behcet's disease who presented with dysarthria and right-sided hemiparesis. T2-weighted and diffusion-weighted images (DWI) showed a hyperintense lesion in the left pons with a relatively decreased apparent diffusion coefficient (ADC). Imaging showed almost complete resolution of the lesion after treatment with prednisolone. The atypical DWI and ADC findings in this case may reflect cytotoxic edema due to excitotoxic brain injury. This case thus illustrates the radiological diversity of neuro-Behcet's lesions.

Quantitative assessment of cerebral blood flow in genetically confirmed spinocerebellar ataxia type 6.

BACKGROUND: Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant cerebellar ataxia caused by CAG trinucleotide expansion. The characteristics of regional cerebral blood flow (rCBF) in SCA6 patients have not been established, whereas it has been reported that decreased rCBF in the cerebrum seems to be a remote effect of cerebellar impairment in other cerebellar disorders. OBJECTIVE: To clarify the characteristics of rCBF, including cerebro-cerebellar relationship, and its correlation with clinical manifestations in patients with genetically confirmed SCA6 using quantitative assessment of rCBF by brain single-photon emission computed tomography (SPECT). DESIGN: Technetium Tc 99m ethyl cysteinate dimer SPECT study using a Patlak plot. Patients Hiroshima University Hospital, Hiroshima, Japan. Ten patients with SCA6 and 9 healthy controls. Main Outcome Measure The rCBF of the cerebellar vermis, cerebellar hemisphere, and frontal lobes. RESULTS: In SCA6 patients, rCBF was decreased only in the cerebellar vermis and hemisphere compared with healthy controls, and this was inversely correlated with duration of illness. The rCBF in the frontal lobes was slightly correlated with duration of illness without statistical significance. The rCBF in the vermis was inversely correlated with severity of dysarthria, but there was no significant correlation with CAG repeated expansions. CONCLUSIONS: Decrease in rCBF was found only in the cerebellum and was associated with duration of illness, dysarthria and ataxia, and cerebellar atrophy. No remote effect of cerebellar hypoperfusion was found in the SCA6 patients.

Frequency of asymptomatic microbleeds on T2*-weighted MR images of patients with recurrent stroke: association with combination of stroke subtypes and leukoaraiosis.

BACKGROUND AND PURPOSE: Asymptomatic microbleeds shown by T2*-weighted MR imaging are associated with small-artery diseases, especially with intracerebral hemorrhage. Few studies have focused on the prevalence of microbleeds in patients with recurrent stroke. We investigated frequency of microbleeds in patients with recurrent stroke and association of presence of microbleeds with a combination of stroke subtypes and severity of leukoaraiosis. METHODS: The study population consisted of 102 patients with primary stroke and 54 patients with recurrent stroke. Microbleeds were counted and classified by using T2*-weighted MR imaging with a 1.0-T system. RESULTS: Patients with recurrent stroke showed a significantly higher prevalence of microbleeds (68.5%) than did patients with primary stroke (28.4%) (P <.0001). Among patients with recurrent stroke, the highest frequency of microbleeds occurred in those with intracerebral hemorrhage alone (92.3%), with the next highest frequency occurring in those with a combination of intracerebral hemorrhage and ischemic stroke (76.5%) and then those with ischemic stroke alone (50.0%) (P <.05). Leukoaraiosis was more severe in patients with recurrent stroke than in patients with primary stroke, and correlations between grade of microbleeds and severity of leukoaraiosis were found in patients with primary stroke (r = 0.367, P <.001) and in patients with recurrent stroke (r = 0.553, P <.0001). Logistic regression analysis identified recurrent stroke (odds ratio, 4.487; 95% confidence interval, 1.989-10.120) and leukoaraiosis (odds ratio, 5.079; 95% confidence interval, 2.125-12.143) as being significantly and independently associated with microbleeds. CONCLUSION: Asymptomatic microbleeds are observed to occur frequently in patients with recurrent stroke, either hemorrhagic or ischemic stroke, and are closely associated with the severity of leukoaraiosis.

Magnetization transfer measurements of brain structures in patients with multiple system atrophy.

To determine whether magnetization transfer imaging (MTI) demonstrates abnormalities in the brain structures of patients with multiple system atrophy (MSA), we examined 12 patients with clinically probable MSA and 11 control subjects. We calculated magnetization transfer ratios (MTRs) using region of interest analysis from MTI and assessed abnormal signal changes on T2-weighted images. MTRs of the base of the pons, middle cerebellar peduncle, putamen, and white matter of the precentral gyrus were significantly lower in the MSA patients than in the controls. Abnormal signal changes on T2-weighted images were observed in the base of the pons (n = 6), middle cerebellar peduncle (n = 7), and putamen (n = 7). MTRs of regions with abnormal signals were significantly lower than those of regions without abnormal signals and those in the controls. Even the MTRs of the regions without abnormal signals were lower than those in the controls. MTRs of the pyramidal tract, including white matter of the precentral gyrus, posterior limb of the internal capsule, cerebral peduncle, and base of the pons, were significantly lower in patients with pyramidal tract sign (n = 7) than in the controls. Patients with asymmetrical parkinsonism (n = 5) showed significantly lower MTRs in the putamen contralateral to the predominant side of parkinsonian symptoms than the ipsilateral side, although asymmetry of abnormal signal changes on T2-weighted images was not evident in more than half of those patients. This study showed that MTI demonstrates abnormalities in the brains of patients with MSA that seem to reflect underlying pathological changes and that the pathological changes detected by MTI seem to give rise to clinical symptoms. This study also showed that the abnormalities are detected more sensitively and over a larger area by MTI than by conventional magnetic resonance imaging.

Magnetization transfer measurements of cerebral white matter in patients with myotonic dystrophy.

To determine whether patients with myotonic dystrophy (MyD) have structural changes in the cerebral white matter, we performed magnetization transfer (MT) imaging of the cerebral white matter in 14 MyD patients and 11 age-matched normal controls. We calculated MT ratios in both the white matter lesions (WMLs) and the normal-appearing white matter (NAWM) of MyD patients using region of interest (ROI) analysis. MT ratios in WMLs were markedly decreased, and all ROIs in NAWM also showed significantly lower MT ratios in MyD patients than in normal controls. The average MT ratio of all ROIs in WMLs and NAWM in each patient showed a significant negative correlation with duration of illness, but not with the patient's age or age at onset. The results of the present study indicate not only the presence of pathological changes in WMLs but also the widespread involvement of NAWM in MyD patients. The results also suggest that structural changes in the white matter may be progressive during the clinical course of MyD.