[A case of recurrent non embolic stroke with non-fluent aphasia due to polycythemia vera].

A 79-year-old woman was admitted to our hospital with a diagnosis of acute noncardioembolic stroke on division of the left middle cerebral artery with non-fluent aphasia. Although she was treated with dual antiplatelet therapy of aspirin and clopidogrel at first, she suffered a second stroke with enlargement of the same stroke lesion and worsening aphasia symptoms. There were only 46 days between the initial onset and recurrent stroke event.She had been diagnosed with polycythemia vera (PV) based on an increase in the blood cell count and a JAK2 mutation. The administration of hydroxyurea was effective for normalizing the blood cell count and preventing stroke recurrence. Cerebral infarction with or without any risk factors accompanied by an elevated blood cell count with a hematocrit value >45% can be PV, so it is necessary to start cytoreductive therapy as soon as possible in such cases.

Retrospective Analysis of Argatroban in 353 Patients with Acute Noncardioembolic Stroke.

BACKGROUND: Argatroban is a thrombin inhibitor agent for acute noncardioembolic ischemic stroke in Japan. We studied the prognosis in patients with acute stroke treated by argatroban in comparison with the control group with ozagrel in our hospital. SUBJECTS AND METHODS: A total of 513 patients with acute noncardioembolic ischemic stroke were enrolled retrospectively from our hospital database. Of all patients with stroke, 353 were administered with argatroban. The other 160 control patients were administered with ozagrel. The patients were examined as to their stroke types, the neurological severity according to the National Institutes of Health Stroke Scale (NIHSS), and clinical outcomes on discharge were determined according to the modified Rankin Scale (mRS). RESULTS: A total of 353 patients with acute noncardioembolic stroke, including 138 with lacunar infarction (LIs) and 215 with atherothrombotic infarction (ATI) showed functional recovery by argatroban, but the effectiveness of argatroban was not superior to ozagrel therapy defined by the control group. A total of 255 patients with ATI who were treated with both argatroban and ozagrel showed improvement by 1 point. We could not find any significant difference between argatroban and ozagrel in the 2 stroke subtypes, LI and ATI. We also found that combination therapy of argatroban and edaravone was not superior to argatroban monotherapy in clinical outcome. CONCLUSIONS: Argatroban therapy was not superior to control with ozagrel therapy in acute noncardioembolic ischemic stroke, including LI and ATI, regardless of the use of edaravone.

Analysis of Recurrent Stroke Volume and Prognosis between Warfarin and Four Non-Vitamin K Antagonist Oral Anticoagulants' Administration for Secondary Prevention of Stroke.

OBJECTIVE: We investigated recurrent stroke volume with nonvalvular atrial fibrillation (NVAF) patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) about clinical backgrounds and number of recurrent stroke. METHODS: We administered 4 NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban in 101 postcardioembolic strokes with NVAF. In a retrospective study, we measured recurrent stroke volume with magnetic resonance imaging volumetric software and compared them between 10 vitamin K anticoagulant (VKA: warfarin) cases and 13 NOAC cases under anticoagulant therapy. RESULTS: Of 101 cases, 31 were started with a VKA and switched to NOACs after 10 recurrent strokes. Other 70 cases were directly started with NOACs and 13 cases with NOACs as first anticoagulants had recurrent stroke. The frequency of recurrent stroke during anticoagulant therapy is not different between the VKA group and the 3 NOACs group. Recurrent stroke volume is significantly larger in the VKA group (26.4 cm3) than in the NOACs group (1.2 cm3). CONCLUSIONS: Secondary prevention with NOACs after stroke might be more beneficial than a VKA by reducing recurrent infarct volume.

Serum Lipid Fractions and Cerebral Microbleeds in a Healthy Japanese Population.

BACKGROUND: Cerebral microbleeds (CMBs) are associated with focal hemosiderin deposits and represent a form of cerebral small vessel disease. To date, indefinite and inconsistent reports are available regarding the association between serum lipid fractions and CMBs. In addition, these previous studies did not include Asian populations, who may have a higher risk of cerebral hemorrhage. The purpose of this study was to examine the associations between serum lipid fractions and CMBs in healthy Japanese subjects. METHODS: We performed a cross-sectional study involving 4,024 neurologically normal Japanese subjects (mean age 61.6 years). All the participants underwent 1.5-Tesla magnetic resonance imaging scan, and CMBs were classified into 3 groups based on their locations. The concentrations of lipid fractions were categorized into quartiles and the association between the lipid fractions and CMBs were investigated using logistic regression analysis. RESULTS: CMBs were observed in 164 (4.1%) of participants. Of these participants with CMBs, 33 (20.1%) had lobar CMBs and 91 (55.5%) had deep CMBs. Subjects with deep CMBs had lower total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels. After adjusting for confounding factors, lower TC and HDL-C levels were still associated with the presence of deep CMBs (OR for the highest vs. the lowest quartiles of TC and HDL-C was 2.28 [95% CI 1.05-4.94], and 1.93 [95% CI 1.02-3.65], respectively). The presence of subcortical infarcts and periventricular hyperintensities was more frequently observed in deep CMBs, whereas white matter hyperintensities were more frequently observed in lobar CMBs. CONCLUSIONS: Our results suggest that low serum TC and HDL-C levels are closely associated with deep CMBs.

The Effectiveness of Repetitive Transcranial Magnetic Stimulation for Poststroke Apathy Is Associated with Improved Interhemispheric Functional Connectivity.

Poststroke apathy is relatively common and has negative effects on the functional recovery of the patient; however, few reports have demonstrated the existence of effective treatments for poststroke apathy. Here, we describe a case of poststroke apathy that was successfully treated with repetitive transcranial magnetic stimulation (rTMS). Using resting-state functional magnetic resonance imaging, we detected improved interhemispheric functional connectivity that was correlated with the patient's recovery from poststroke apathy. Our case suggests that rTMS can improve the transfer of information through the corpus callosum, which is crucial for helping patients recover from poststroke apathy.

Gastroesophageal reflux during enteral feeding in stroke patients: a 24-hour esophageal pH-monitoring study.

BACKGROUND: Patients who are unable to eat or drink after stroke may receive percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Although the most common serious complication is well known to be aspiration pneumonia, the role of gastroesophageal reflux (GER) has not been fully assessed. The aim of this study was to examine, by means of 24-hour esophageal pH monitoring, whether GER is related to aspiration pneumonia and whether the size and laterality of brain lesions influence GER. METHODS: Sixteen stroke patients were examined using a Degitrapper pH400 (Medtronic Japan Co., Tokyo, Japan) and Zinetics 24ME multiuse pH catheter (Medtronic). All patients had stroke lesions in the territory of the left or right middle cerebral artery that were confirmed by magnetic resonance imaging (MRI) and were receiving PEG or nasogastric feeding. Stroke volume was measured with MRIcron software. RESULTS: Nine patients (56%) were diagnosed with GER, and 10 (63%) developed aspiration pneumonia after enteral feeding. The rate of aspiration pneumonia was significantly higher in patients with GER (88.9%) than in those without GER (42.9%; P = .04). Patients with left hemispheric lesions had a significantly higher incidence of acid reflex than those with right lesions (116 ± 105 vs 13 ± 17; P = .04). There were no significant differences in total time of acid reflux or mean pH value between patients with left and right hemispheric lesions. The lesion volume had no significant effect on any of 3 indices of GER. CONCLUSIONS: GER is associated with aspiration pneumonia and occurs more often in patients with stroke lesions in the left hemisphere.

Meningoencephalomyelitis Caused by Brucella Canis: A Case Report and Literature Review.

Human brucellosis, one of the most common zoonoses worldwide, is rare in Japan. Brucella canis is the specific pathogen of human brucellosis carried by dogs. According to an epidemiological study of B. canis infection in Japan, B. canis is the specific pathogen of human brucellosis in dogs. We herein report a rare case of meningoencephalomyelitis caused by B. canis in a 68-year-old Japanese man. Neurobrucellosis was diagnosed based on a serum tube agglutination test and abnormal cerebrospinal fluid findings. The patient was started on targeted treatment with a combination of doxycycline and streptomycin. Although extremely rare, neurobrucellosis should be considered in patients with a fever of unknown origin and unexplained neurological symptoms.

Microbleeds are associated with subsequent hemorrhagic and ischemic stroke in healthy elderly individuals.

BACKGROUND AND PURPOSE: Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals. METHODS: We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject. RESULTS: MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region. CONCLUSIONS: This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.

Post-stroke apathy and hypoperfusion in basal ganglia: SPECT study.

BACKGROUND: Although apathy has been reported as one of the neuropsychiatric symptoms following stroke, there are few studies on regional cerebral blood flow (rCBF) in stroke patients with apathy. The present study compared rCBF between apathetic and non-apathetic patients after stroke. METHODS: We recruited 102 patients with cerebral infarction within 1 month after stroke and performed neuropsychiatric assessments that included the apathy scale. rCBF was quantitatively measured using N-isopropyl-p-(123)I-iodoamphetamine single-photon emission computed tomography. RESULTS: Thirty-seven patients (36%) had apathy. The apathetic group showed lower cognitive function and a higher depressive state than the non-apathetic group. rCBF in the basal ganglia was reduced for the apathetic group compared with the non-apathetic group. Furthermore, lesions in the left basal ganglia were associated with hypoperfusion in bilateral basal ganglia and the presence of apathy. CONCLUSION: These findings demonstrate that apathy is a frequent symptom among stroke patients and that hypoperfusion caused by basal ganglia lesions may contribute to post-stroke apathy.

Multiscale Entropy of Resting-State Functional Magnetic Resonance Imaging Differentiates Progressive Supranuclear Palsy and Multiple System Atrophy.

Distinguishing progressive supranuclear palsy (PSP) from multiple system atrophy (MSA) in the early clinical stages is challenging; few sensitive and specific biomarkers are available for their differential diagnosis. Resting-state functional magnetic resonance imaging (rs-fMRI) is used to study the fluctuations in blood oxygen level-dependent (BOLD) signals at rest, which provides evidence for aberrant brain functional networks in neurodegenerative diseases. We aimed to examine whether rs-fMRI data could differentiate between PSP and MSA via a multiscale entropy (MSE) analysis of BOLD signals, which estimates the complexity of temporal fluctuations in brain activity. We recruited 14 and 18 patients with PSP and MSA, respectively, who underwent neuropsychological tests and rs-fMRI. PSP patients demonstrated greater cognitive function impairments, particularly in the frontal executive function. The bilateral prefrontal cortex revealed lower entropy BOLD signal values in multiple time scales for PSP, compared to the values observed in MSA patients; however, the functional connectivity of the representative brain networks was comparable between the diseases. The reduced complexity of BOLD signals in the prefrontal cortex was associated with frontal dysfunction. Thus, an MSE analysis of rs-fMRI could differentiate between PSP and MSA, and the reduced complexity of BOLD signals could be associated with cognitive impairment.

The association of metabolic syndrome with executive dysfunction independent of subclinical ischemic brain lesions in Japanese adults.

BACKGROUND/AIMS: The aim of this study is to examine whether metabolic syndrome is directly associated with cognitive impairment independent of subclinical ischemic brain lesions. METHODS: We examined 1,543 neurologically normal subjects (44-86 years of age). Metabolic syndrome, brain MRI, and cognitive functions including general cognition and executive function were assessed. RESULTS: After adjusting for silent brain lesions and demographic risk factors, metabolic syndrome was an independent risk factor for impairment of executive function (OR = 1.41, 95% CI = 1.17-1.25 for Kohs' Test; OR = 2.25, 95% CI = 1.64-3.07 for Frontal Assessment Battery). Among the components of metabolic syndrome, elevated fasting glucose was the only independent risk factor for impairment of executive function. CONCLUSION: Metabolic syndrome is associated with impairment of executive function independent of silent brain lesions in the Japanese population.

Metabolic syndrome is associated with silent ischemic brain lesions.

BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is a recognized risk factor for stroke, but it is unclear whether MetS is also related to subclinical ischemic lesions. We examined the association of MetS with the prevalence of silent brain infarction, periventricular hyperintensity, and subcortical white matter lesions in healthy adults. METHODS: We conducted a cross-sectional study in 1151 Japanese healthy subjects. Three types of silent lesions were assessed by MRI scans. MetS was diagnosed using the criteria by the National Cholesterol Education Adult Treatment Panel III. RESULTS: After adjusting for age and other factors, MetS was significantly associated with silent brain infarction, periventricular hyperintensity and subcortical white matter lesions. Among the MetS components, elevated blood pressure was commonly associated with all types of lesions. Dyslipidemia and elevated fasting glucose levels were associated with subcortical white matter lesions and periventricular hyperintensities, respectively. Positive trends were observed between the number of MetS components and prevalence of silent lesions. CONCLUSIONS: MetS is associated with the prevalence of silent lesions independent of other risk factors. The clustering of MetS components tends to increase the prevalence of silent lesions.

[The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults].

AIM: We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. METHODS: MRI scans were performed on 109 neurologically normal adults (mean age, 58.6+/-5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. RESULTS: There were no differences in age, sex, dyslipidemia, BMI, smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. CONCLUSION: The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation.

Metabolic syndrome is associated with incidence of deep cerebral microbleeds.

Metabolic syndrome (MetS) has been associated with silent brain lesions; however, there are no data on the relationship between MetS and the incidence of cerebral microbleeds (CMBs) in Asian populations. The aim of this study was to evaluate the longitudinal association between MetS and incidence of CMBs in the Japanese population. We performed a prospective cohort study involving 684 Japanese participants (mean age, 61.7 years) with a mean 6.5 ± 3.4 years follow-up. All participants underwent 1.5 T magnetic resonance imaging, and CMBs were classified by their locations. Logistic regression analyses were performed to examine the relationship of MetS and its components with the incidence of CMBs. MetS was observed in 7.5% of the study population. Forty-nine (7.2%) subjects (36 had new deep or infratentorial CMBs, 13 had new strictly lobar CMBs) developed new CMBs during the follow-up period. In multivariable analysis, MetS was significantly associated with the incidence of deep or infratentorial CMBs (odds ratio, 4.03; 95% confidence interval, 1.72-9.41), and the elevated blood pressure component was most robustly associated with the incidence of deep or infratentorial CMBs (odds ratio, 5.16; 95% confidence interval, 2.02-13.2). Increased body mass index was also associated with incidence of deep or infratentorial CMBs (odds ratio, 2.45; 95% confidence interval, 1.06-5.67). The present study showed that MetS predicts incidence of CMBs in the deep brain regions and high blood pressure is the most important among the MetS components.

Differentiating Alzheimer's disease from subcortical vascular dementia with the FAB test.

BACKGROUND: The frontal assessment battery (FAB) test is a composite tool for assessing executive functions related to the frontal lobe. Neuropsychological and blood-flow studies indicate distinct patterns of deterioration of anterior and posterior cortical function in Alzheimer's disease (AD) and subcortical vascular dementia (VD) patients. We predict that the FAB score may be useful for discriminating VD from AD. OBJECTIVE: To evaluate the clinical usefulness of the FAB test for differential diagnosis of AD and VD. METHODS: We compared FAB scores in 25 patients with AD, 27 patients with VD, and 80 age-matched normal control subjects. The AD group was matched for age, education and MMSE score with the VD group. The subtest scores in FAB were also compared among the three groups. RESULTS: The FAB scores were significantly decreased in both the AD and VD groups compared to the control group, and the reduction were greater in the VD group. Among the FAB subtests, mental flexibility (phonological verbal fluency) was the only subtest that significantly discriminated VD from the other two groups. CONCLUSIONS: The FAB test can provide useful information for differentiating AD and VD at the bedside.

Effect of one-shot intravenous 0.42 mega unit urokinase therapy in patients with acute ischemic stroke.

We evaluated the efficacy of intravenous (IV) urokinase (UK) treatment for acute ischemic stroke patients. We treated 45 patients with 0.42 mega units of IV UK and 201 patients with other conventional agents. Clinical severity and outcome were evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and modified Rankin scale (mRS). We defined clinical improvement as a reduction of NIHSS score of > 4 points between admission and discharge. The rate of improvement, as defined earlier, was significantly higher in the UK group (27/45; 60%) than in the non-UK group (67/201, 33%) (P = .0009; chi(2) test). The rate of mRS 0-2 (good outcome) on discharge in the UK group (28/45; 62%) was slightly (but not significantly) higher than that in the non-UK group (99/201; 49%). Baseline characteristics, including risk factors, did not differ between the 2 groups, except for time to treatment and length of hospitalization. We conclude that treatment of acute ischemic stroke patients with 0.42 mega units of IV UK shows better clinical improvement than conventional therapy.

Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study.

Silent brain infarction (SBI) and white matter lesions (periventricular hyperintensity [PVH] and subcortical white matter lesions [SWML] are detected in both stroke patients and normal elderly persons. We prospectively examined the association between these lesions and the risk of subsequent stroke and mortality in neurologically normal adults. Magnetic resonance imaging scans were performed in 2,684 neurologically normal subjects with no history of stroke (mean age, 58 +/- 7 years old at entry) who underwent our health screening of the brain. After the brain screening, we obtained information about clinical stroke onset and death using a questionnaire sent annually to all subjects. When a subject suffered from medical events, we confirmed the detailed information in a telephone interview and by asking the attending physician. SBI was defined as a focal T2-hyperintensity and T1-hypointensity lesion > 3 mm. PVH and SWML were graded according to their severity. The average follow-up period was 6.3 years. Stroke occurred in 102 subjects (3.8%), and 93 subjects died during follow-up. The incidence of clinical stroke was significantly higher in the subjects with SBI than in those without SBI. Marked PVH and marked SWML independently increased the risk of stroke (for SBI, stroke risk factor-adjusted odds ratio [OR] = 3.66, 95% confidence interval [CI] = 2.28-5.89; for marked PVH, stroke risk factor-adjusted OR = 2.08, 95% CI = 1.04-4.17; for marked SWML, stroke risk factor-adjusted OR = 2.73, 95% CI = 1.32-5.63). Regarding mortality, SBI and marked PVH increased the risk of death (for SBI, stroke risk factor-adjusted OR = 1.95, 95% CI = 1.16-3.29; for PVH, stroke risk factor-adjusted OR = 4.01, 95% CI = 1.91-8.45). Death attributable to stroke occurred more frequently in those subjects with SBI, marked PVH, and marked SWML. We conclude that SBI, marked PVH, and marked SWML are important risk factors for clinical stroke and that SBI and marked PVH also increase the risk of mortality.

[Clinical characteristics and prognosis in stroke patients with diabetes mellitus: retrospective evaluation using the Japanese Standard Stroke Registry database (JSSRS)].

We studied clinical characteristics and prognosis in acute stoke patients with diabetes mellitus registered on the Japanese Standard Stroke Registry database. A total of 16,630 acute stroke patients admitted to 56 hospitals in Japan. They were examined as to their stroke types, risk factors, their severity of stroke according to the NIH Stroke Scale (NIHSS) and Japan Stroke Scale (JSS), and outcomes by the modified Rankin Scale (m-RS). The incidence of subarachnoid hemorrhage was relatively high in the group of patients who had neither hypertension nor diabetes, and the incidence of brain hemorrhage was higher in the group of patients who had hypertension without diabetes. The frequencies of lacunar infarct and atherothrombotic infarct were also higher in the group of patients who had both hypertension and diabetes. In the diabetic group without hypertension, there were less numbers of hemorrhagic stroke. The ratio of good prognosis (m-RS 0-1) was significantly smaller in the diabetic patients with lacunar infarction, cardioembolic infarction, and subarachnoid hemorrhage. Additionally, there was significantly more stroke recurrence in the diabetic patients (33.0% vs. 26.9%, p<0.0001). The diabetic patients who received insulin therapy (-0.8 +/- 7.4), diet therapy (-0.4 +/- 9.4), or oral medicine (-0.9 +/- 7.2), showed significantly less improvements in the NIHSS compared to the non-diabetic patients (-1.6 +/- 8.2), respectively. Moreover, the poor-management diabetic patients showed significantly less improvements in the JSS compared to non diabetic patients (3.8 +/- 7.7 vs. 4.8 +/- 8.6, p<0.005). In conclusions, stroke patients with diabetes mellitus showed more stroke recurrence and resulted in poorer functional recovery compared to patients without diabetes.

[Effect of sarpogrelate in enteral feeding of patients with gastroesophageal reflux (GER)].

AIM: Enteral feeding of patients who are unable to eat or drink because of neurological disorders finally undergo percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Their most common serious complication is aspiration pneumonia. Our objectives were to evaluate the effect of sarpogrelate (a 5-HT2A receptor blocker) on gastroesophageal reflux (GER) in these patients. METHODS: This study was performed in 5 elderly patients, aged 70-87 years with neurological disorders (stroke 4, post herpes encephalitis 1), on PEG or nasogastric feeding for 5 weeks-1 year. A 48-hour esophageal pH study was performed using the Degitrapper pH400 (Medtronic Co.). The pH monitor catheter was passed into the esophagus transnasally and positioned with the pH electrode 5cm above the lower esophageal sphincter. During the first 24 hours drug no drug was given, and during the next 24 hours we gave 100mg sarpogrelate 3 times. We analyzed the frequency of acid reflux (when the pH in the esophagus become less than 4.0 for more than 5 seconds, we defined this is 1 episode of acid reflux), frequency of acid reflux and mean pH values between drug-on and drug-off periods. An upright position was maintained for two hours after each meal. RESULTS: When the results of pH monitoring during two half days (from 7 pm to 7 am: 12 hours) was compared between drug-on term and drug-off term, mean pH value was statistically elevated from 6.0 +/- 0.2 (drug-off) to 6.5 +/- 0.4 (drug-on) (mean +/- SD, p< 0.05). Frequency and the total time of acid reflex showed no difference between the two periods. CONCLUSION: Treatment with sarpogrelate might be effective in patients with GER by blocking activated serotonin receptor in the gastrointestinal system.