Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial.

Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258­0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206­2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Incipient progressive supranuclear palsy is more common than expected and may comprise clinicopathological subtypes: a forensic autopsy series.

We investigated 998 serial Japanese forensic autopsy cases (0-101 years old, mean age 61.7 ± 21.9), with no case selection, using immunohistochemistry to detect cases with progressive supranuclear palsy (PSP). Twenty-nine cases (mean age 82.3 ± 7.2 years, 11 males, 18 females) fulfilled the National Institute of Neuronal Disorders and Stroke (NINDS)-PSP pathological criteria (2.9% of all cases, 4.6% of cases over 60). All had neuronal and glial inclusions in the basal ganglia and brainstem. However, 13 cases had low tau pathology and were categorized as atypical PSP. In addition to PSP pathology, multiple types of astrocytic inclusions and comorbid proteinopathies, particularly a high prevalence of argyrophilic grain disease, were found. All cases had not been diagnosed with PSP and had preserved daily functioning prior to death. However, 14 (48.3%), 11 (37.9%), and 16 (55.2%) cases showed signs of dementia, depressive state, and gait disturbance, respectively. Sixteen accidental death cases (55.2%), including from falls and getting lost, and 11 suicide cases (37.9%) appear to have a relationship with incipient PSP pathology. Cluster analysis using the distribution and amount of 4-repeat-tau pathology classified the cases into three subgroups: Group 1 (10 cases) had typical PSP pathology and seven cases (70.0%) had dementia as the most frequent symptom; Group 2 (7 cases) had significantly higher frequency of gait disorder (6 cases, 85.7%), and less neocortical tau pathology than Group 1; Group 3 (12 cases) had relatively mild PSP pathology and high argyrophilic grain burdens. Granular-shaped astrocytes were the dominant astrocytic inclusion in all cases. We conclude that in forensic cases incipient PSP occurs with a higher prevalence than expected. If these findings can be extrapolated to other population-based cohorts, PSP may be more common than previously thought.

A Novel Imaging Technique (X-Map) to Identify Acute Ischemic Lesions Using Noncontrast Dual-Energy Computed Tomography.

BACKGROUND: We evaluated whether X-map, a novel imaging technique, can visualize ischemic lesions within 20 hours after the onset in patients with acute ischemic stroke, using noncontrast dual-energy computed tomography (DECT). MATERIALS AND METHODS: Six patients with acute ischemic stroke were included in this study. Noncontrast head DECT scans were acquired with 2 X-ray tubes operated at 80 kV and Sn150 kV between 32 minutes and 20 hours after the onset. Using these DECT scans, the X-map was reconstructed based on 3-material decomposition and compared with a simulated standard (120 kV) computed tomography (CT) and diffusion-weighted imaging (DWI). RESULTS: The X-map showed more sensitivity to identify the lesions as an area of lower attenuation value than a simulated standard CT in all 6 patients. The lesions on the X-map correlated well with those on DWI. In 3 of 6 patients, the X-map detected a transient decrease in the attenuation value in the peri-infarct area within 1 day after the onset. CONCLUSIONS: The X-map is a powerful tool to supplement a simulated standard CT and characterize acute ischemic lesions. However, the X-map cannot replace a simulated standard CT to diagnose acute cerebral infarction.

[Comprehensive Hybrid Strategy for Carotid Artery Stenosis with 8 Rules "Toyama Carotid 8"].

In this paper, the preliminary results of carotid endarterectomy(CEA)and carotid artery stenting(CAS)for patients with carotid artery stenosis based on the 8 Rules "Toyama Carotid 8" are reported. This study included 104 patients who underwent CEA or CAS for carotid artery stenosis between March 2012 and January 2015. Toyama 8 Rules primarily recommend CEA and CAS for symptomatic and asymptomatic lesions, respectively. However, crossover of therapeutic options can be performed in patients at high surgical risk associated with CEA or CAS. Monitoring of platelet function is important prior to CAS. Internal shunting and near infrared spectroscopy monitoring are essential in CEA. Temporary cardiac pacing is essential in CAS. The choice of protection device and stent depends on the results of MR plaque imaging. Cerebral blood flow measurement is mandatory before and after CEA/CAS. Fifty-two CEAs and 52 CASs were performed for 55 symptomatic and 49 asymptomatic lesions. Crossover of therapeutic options was performed in 10(18%)of 55 symptomatic lesions and 7(14%)of 49 asymptomatic lesions. The 30-day morbidity rate was 1.9% in CEA and 1.9% in CAS. Postoperative diffusion-weighted magnetic resonance imaging showed fresh ischemic lesions in 5 patients who underwent CEA(10%)and 9 who underwent CAS(17%). Hyperperfusion syndrome occurred in one patient(1.0%). A management protocol for carotid artery stenosis needs to be established in hospitals to allow sharing of information and improvement in the short-term results of CEA / CAS for carotid artery stenosis. Further studies are warranted to evaluate the long-term outcome.

Dabigatran and factor Xa inhibitors for stroke prevention in patients with nonvalvular atrial fibrillation.

Stroke is a major health problem worldwide, and is often fatal or associated with poor long-term outcomes. Atrial fibrillation (AF) is responsible for up to 20% of all strokes; and the risk of stroke in patients with AF increases with age. Although warfarin is well established for the prevention of stroke in patients with AF, it has some limitations, particularly a narrow therapeutic window, variable/unpredictable pharmacokinetic/pharmacodynamic properties, the restriction of vitamin K intake, and the need for regular coagulation monitoring. Therefore, warfarin is underused for stroke prevention in patients with AF. Several anticoagulants that inhibit thrombin or factor Xa have been developed. Dabigatran is a direct thrombin (factor IIa) inhibitor that overcomes many of the limitations associated with warfarin. The recent Randomized Evaluation of Long Term Anticoagulant Therapy study showed the noninferiority of 110 mg and 150 mg dabigatran twice daily, and the superiority of 150 mg dabigatran twice daily versus adjusted-dose warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular AF. In addition, the rate of intracranial hemorrhage was much lower with both doses of dabigatran than with warfarin. Dabigatran was recently approved in Japan for the prevention of ischemic stroke and systemic embolism in patients with nonvalvular AF. Therefore, in this review, we discuss the properties of dabigatran and its clinical efficacy, safety, and positioning in the prevention of stroke. We also discuss precautions for the use of dabigatran and future perspectives with a view to reducing the risk of stroke with new oral anticoagulants, including factor Xa inhibitors in AF patients.

Study of hemostatic biomarkers in acute ischemic stroke by clinical subtype.

BACKGROUND: We studied the usefulness of hemostatic biomarkers in assessing the pathology of thrombus formation, subtype diagnosis, prognosis in the acute phase of cerebral infarction, and differences between various hemostatic biomarkers. METHODS: Our study included 69 patients with acute cerebral infarction who had been hospitalized within 2 days of stroke onset. Fibrin monomer complex (FMC), soluble fibrin (SF), D-dimer, thrombin-antithrombin III complex, fibrinogen, antithrombin III, and fibrin/fibrinogen degradation products (FDPs) were assayed as hemostatic biomarkers on days 1, 2, 3, and 7 of hospitalization. RESULTS: In the cardioembolic (CE) stroke group, FMC and SF levels were significantly higher on days 1 and 2 of hospitalization, and D-dimer levels were significantly higher on day 1 of hospitalization, compared to the noncardioembolic (non-CE) stroke group. FDP levels were significantly higher at all times in the CE group compared to the non-CE group. Neither the National Institute of Health Stroke Scale (NIHSS) used during hospitalization nor the modified Rankin Scale (mRS) used at discharge found any significant correlations to hemostatic biomarkers, but the NIHSS score during hospitalization was significantly higher in the CE group than in the non-CE group. CONCLUSIONS: Measurements of hemostatic biomarkers, such as FMC, SF, and D-dimer on the early stage of cerebral infarction are useful for distinguishing between CE and non-CE stroke.

One-year atherothrombotic vascular events rates in outpatients with recent non-cardioembolic ischemic stroke: the EVEREST (Effective Vascular Event REduction after STroke) registry.

BACKGROUND: Patients with recent ischemic stroke may have higher risk of atherothrombosis than stable patients with established vascular events. Our aims were to investigate 1-year atherothrombotic vascular event rates and to assess the risk factors for recurrent ischemic stroke in this population. METHODS: This prospective cohort study was conducted between January 2007 and July 2009 at 313 hospitals in Japan. Outpatients who were at least 45 years of age and who had received oral antiplatelet therapy were enrolled within 2 weeks to 6 months from the last onset of noncardioembolic ischemic stroke. At 12 ± 3 months after enrollment, data on presence/absence of atherothrombotic vascular events were collected. The primary endpoint was the occurrence of fatal or nonfatal ischemic stroke. RESULTS: A total of 3452 patients were enrolled, and 3411 patients who had baseline data were included in the analysis. The 1-year event rate was 3.81% (95% confidence interval 3.15-4.48%) for fatal or nonfatal ischemic stroke and 0.84% (95% confidence interval 0.52-1.15%) for all-cause mortality. The annual rate of recurrent ischemic stroke was significantly higher in patients who had ischemic stroke at least twice than in patients who had first-ever ischemic stroke (5.02% vs 3.59%; P = .0313). In the multivariable Cox regression analysis, recurrent ischemic stroke was significantly associated with age (P = .0033), the presence of diabetes (P = .0129), and waist circumference ≥80 cm (P = .0056). CONCLUSIONS: Patients with recent ischemic stroke have a higher risk of stroke recurrence than stable patients enrolled in the REduction of Atherothrombosis for Continued Health (REACH) registry even though they received antiplatelet therapy. The rigorous management of risk factors is needed.

Bilateral subthalamic deep brain stimulation for camptocormia associated with Parkinson's disease.

BACKGROUND: Few multiple case studies of the effects of deep brain stimulation for camptocormia associated with Parkinson's disease have been reported. Although deep brain stimulation was in some cases not effective against camptocormia, it is unclear in which types of patients it was effective in treating camptocormia. OBJECTIVE: We treated 4 Parkinson's disease patients with camptocormia and evaluated their paraspinal muscle status by computed tomography to specify the characteristics of cases of effective treatment. METHODS: The 2 female and 2 male patients in this study were 60-69 years old, with a disease duration from onset to surgery of 7-13 years and a follow-up period of 18-40 months. The electrodes were implanted bilaterally in the subthalamic nuclei. RESULTS: Camptocormia was improved in 3 cases, and was unchanged in the remaining case although other parkinsonian symptoms improved. The computed tomography number of paraspinal muscle in the unimproved patient was much smaller than that in the improved patients. CONCLUSIONS: A relationship may exist between improvement of camptocormia and severity of paraspinal muscle degeneration.

[A case of anti-N-methyl-D-aspartate receptor encephalitis with ovarian teratoma showing excellent recovery with decreasing of anti-N-methyl-D-aspartate receptor antibody].

We report a case of a 17-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms. Pelvic MRI revealed a right ovarian tumor that was suspected of being an ovarian teratoma. On the 27th day after onset, the patient underwent right salpingo-oophorectomy. The histopathological diagnosis was immature ovarian teratoma. Subsequently, 4 double filtration plasmapheresises (DFPP) were performed from day 34 to day 43. Methylprednisolone (1,000 mg/day for 3 days) was started on day 38. With these treatments, consciousness disturbance completely improved, and the patient was discharged on day 50. The serum and cerebrospinal fluid were positive for antibodies against the GluRzeta1 (NR1)-EGFP/GluRepsilon2 (NR2B) heteromer and the GluRzeta1 (NR1) subunit of NMDAR. The patient was hence diagnosed as having anti-NMDAR encephalitis with ovarian teratoma Serial analysis show that the antibodies against NMDAR decreased with improvement of symptoms after the immunotherapy including DFPP treatment.

Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis.

Background Long-term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high-risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23-0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26-0.91) were lower in DAPT than SAPT, whereas the risk of severe or life-threatening bleeding (HR, 0.72; 95% CI, 0.12-4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370.

[Case of branch atheromatous disease presenting capsular warning syndrome].

We report a case of branch atheromatous disease (BAD) presenting capsular warning syndrome, who subsequently showed a complete recovery by the combination therapy as described below. A 54-year-old man with untreated hypertension was admitted to our hospital because of dysarthria and right hemiplegia. The NIHSS on admission was 12 points, but his symptoms soon completely disappeared during examination. After admission administration of aspirin, heparin, atorvastatin and t-PA were started, but stereotyped episodes of dysarthria and the right hemiplegia occurred repeatedly. We added plasma expander, and he thereafter revealed no further ischemic episodes at 22 hours from admission. Over all, he had 15 times of transient ischemic attack with no lasting deficit. The DWI scan obtained 5 hours after the onset demonstrated a high-intensity region in the left putamen to corona radiata. MRA showed no significant abnormalities. He had been diagnosed as having branch atheromatous disease with capsular warning syndrome. The present case suggests that combination therapy including t-PA and plasma expander may be effective to BAD presenting capsular warning syndrome.

Dual antiplatelet therapy using cilostazol for secondary prevention in patients with high-risk ischaemic stroke in Japan: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Although dual antiplatelet therapy with aspirin and clopidogrel reduces early recurrence of ischaemic stroke, with long-term use this type of therapy is no longer effective and the risk of bleeding increases. Given that cilostazol prevents stroke recurrence without increasing the incidence of serious bleeding compared with aspirin, we aimed to establish whether dual antiplatelet therapy involving cilostazol is safe and appropriate for long-term use. METHODS: In a multicentre, open-label, randomised controlled trial across 292 hospitals in Japan, patients with high-risk non-cardioembolic ischaemic stroke identified on MRI were randomly assigned to two groups in a 1:1 ratio to receive monotherapy with either oral aspirin (81 or 100 mg, once per day) or clopidogrel (50 or 75 mg, once per day) alone, or a combination of cilostazol (100 mg, twice per day) with aspirin or clopidogrel. Randomisation was done centrally (using block randomisation with a block size of six per each participating hospital) through a web-based registration system and was done by EPS Corporation. The patients were required to have at least 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk factors. Trial medication was continued for half a year or longer, for a maximum of 3·5 years. The primary efficacy outcome was the rate of first recurrence of symptomatic ischaemic stroke. Safety outcomes were severe or life-threatening bleeding; any adverse events; serious adverse events; and any bleeding events. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the as-treated population. This trial was registered with ClinicalTrials.gov (number NCT01995370) and UMIN Clinical Trials Registry (number 000012180). FINDINGS: Participants were recruited from Dec 13, 2013, to March 31, 2017. 932 patients assigned to the dual therapy group and 947 patients assigned to the monotherapy group were included in the intention-to-treat analysis. The trial was stopped after the enrolment of 1884 patients of an anticipated 4000 patients because of the delay in recruitment. Ischaemic stroke recurred in 29 (3%) of 932 patients (annualised rate 2·2%) on dual therapy including cilostazol and 64 (7%) of 947 patients (annualised rate 4·5%) on monotherapy during a median 1·4 years follow-up (hazard ratio [HR] 0·49, 95% CI 0·31-0·76, p=0·0010). Severe or life-threatening bleeding occurred in eight patients (annualised rate 0·6%) on dual therapy and 13 patients (annualised rate 0·9%) on monotherapy (HR 0·66, 95% CI 0·27-1·60, p=0·35). Occurrence of any type of adverse event was similar between the groups (255 [28%] of 910 patients in the dual therapy group vs 219 [24%] of 921 patients in the monotherapy group); as was occurrence of serious adverse events (87 [10%] vs 142 [15%]) and bleeding events (38 [4%] vs 33 [4%]). Gastrointestinal bleeding, which affected nine (<1%) of 910 patients in the monotherapy group and nine (<1%) of 921 patients in the dual therapy group, was the most common type of bleeding. INTERPRETATION: The combination of cilostazol with aspirin or clopidogrel had a reduced incidence of ischaemic stroke recurrence and a similar risk of severe or life-threatening bleeding compared with treatment with aspirin or clopidogrel alone in patients at high risk for recurrent ischaemic stroke. FUNDING: Otsuka Pharmaceutical.

Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells.

Causative genes in patients with idiopathic basal ganglia calcification (IBGC) (also called primary familial brain calcification (PFBC)) have been reported in the past several years. In this study, we surveyed the clinical and neuroimaging data of 70 sporadic patients and 16 families (86 unrelated probands in total) in Japan, and studied variants of PDGFB gene in the patients. Variant analyses of PDGFB showed four novel pathogenic variants, namely, two splice site variants (c.160 + 2T > A and c.457-1G > T), one deletion variant (c.33_34delCT), and one insertion variant (c.342_343insG). Moreover, we developed iPS cells (iPSCs) from three patients with PDGFB variants (c.160 + 2T > A, c.457-1G > T, and c.33_34 delCT) and induced endothelial cells. Enzyme-linked immunoassay analysis showed that the levels of PDGF-BB, a homodimer of PDGF-B, in the blood sera of patients with PDGFB variants were significantly decreased to 34.0% of that of the control levels. Those in the culture media of the endothelial cells derived from iPSCs of patients also significantly decreased to 58.6% of the control levels. As the endothelial cells developed from iPSCs of the patients showed a phenotype of the disease, further studies using IBGC-specific iPSCs will give us more information on the pathophysiology and the therapy of IBGC in the future.

Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial.

BACKGROUND AND PURPOSE: The JELIS trial examined the preventive effect of eicosapentaenoic acid (EPA) against coronary artery diseases. Hypercholesterolemic patients received statin only (no EPA group: n=9319) or statin with EPA (EPA group: n=9326) for around 5 years. EPA significantly suppressed the incidence of coronary events in previous analysis. Herein, we investigated the effects of EPA on the primary and secondary prevention of stroke. METHODS: We conducted a subanalysis of JELIS with respect to stroke incidence in the primary and secondary prevention subgroups defined as those without and with a prior history of stroke using Cox proportional hazard ratios, adjusted for baseline risk factor levels. RESULTS: As for primary prevention of stroke, this occurred in 114 (1.3%) of 8862 no EPA group and in 133 (1.5%) of 8841 EPA group. No statistically significant difference in total stroke incidence (Hazard Ratio, 1.08; 95% confidence interval, 0.95 to 1.22) was observed between the no EPA and the EPA groups. In the secondary prevention subgroup, stroke occurred in 48 (10.5%) of 457 no EPA group and in 33 (6.8%) of 485 EPA group, showing a 20% relative reduction in recurrent stroke in the EPA group (Hazard Ratio, 0.80; 95% confidence interval, 0.64 to 0.997). CONCLUSIONS: Administration of highly purified EPA appeared to reduce the risk of recurrent stroke in a Japanese population of hypercholesterolemic patients receiving low-dose statin therapy. Further research is needed to determine whether similar benefits are found in other populations with lower levels of fish intake. The trial is registered at ClinicalTrials.gov (number NCT00231738).

[Case of antiamphiphysin antibody-positive stiff-person syndrome with breast cancer diagnosed by FDG-PET].

We report a case of antiamphiphysin antiboddy-positive stiff-person syndrome associated with breast cancer, which was detected only by FDG-PET. A 46-year-old woman was admitted to our hospital because of painful muscle cramp and stiffness of both legs. Laboratory results were negative for anti-GAD antibody, but highly positive for antiamphiphysin antibody (1: 61,440). She had been diagnosed as having paraneoplastic stiff-person syndrome. However, mammogram, thoracic CT, breast MRI and ultrasonic echography showed no abnormal findings. A whole-body fluorodeoxyglucose (FDG) PET was performed, showing an increased uptake in the left axillary lymph nodes. Then, the left axillary lymph nodes were resected and immunohistochemically diagnosed as breast adenocarcinoma. Treatment of stiff-person syndrome was initiated with corticosteroids followed by chemotherapy against breast cancer, which led to a remarkable improvement of her neurological symptoms. If there is possibility of paraneoplastic syndromes like stiff-person syndrome, FDG-PET is very useful for detecting the occult carcinoma.

[Two cases of cardioembolic stroke with stepwise progression].

We reported two patients of cardioembolic stroke with stepwise progression. Magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) showed narrowing of the middle cerebral artery (MCA) in both patients at the acute phase of onset. Case 1 was classified as "undetermined" based on the TOAST classification although his electrocardiogram revealed atrial fibrillation. Case 2 was classified as "large artery atherosclerosis" with no evidence of cardioembolic source at the acute phase of onset. Follow-up MRA was performed at seventeen days after the onset in case 1 and ten days after the onset in case 2 respectively, which showed complete recanalization of the MCA in each case. The presence of cardioembolic source was also detected in both patients at that time, resulting in the final diagnosis of cardioembolic stroke. Cardioembolic stroke may occasionally present in a stepwise manner suggesting a thrombotic process. When MRA shows stenosis or occlusion of the arteries supplying the cortical areas at the acute phase of onset, it is advisable to examine recanalization of these arteries by follow-up MRA with simultaneous efforts to find out the possible embolic source.

[A case of apical hypertrophic cardiomyopathy complicated by cardiogenic cerebral embolism].

We report a patient with apical hypertrophic cardiomyopahty (AHCM) complicated by a cardiogenic cerebral embolism. A 56-year-old man was admitted to our hospital because of a transient ischemic attack. He had been diagnosed as having AHCM at the age of 39 years. The intravenous administration of heparin was immediately started; however, he developed a weakness in his right fingers on the second day. A brain MRI examination showed multiple small infarctions in the cortex of the left frontal and temporal lobes. Transthoracic echocardiography revealed the hypokinetic movement of the myocardium and a thrombus in the apex. We suspected that the hypertrophic apex had become dilated, causing the formation of the thrombus. He then developed a cardiogenic cerebral embolism. The thrombus in the apex disappeared after the continuous administration of heparin intravenously. Here, we emphasize that patients with AHCM in the dilatation phase must receive warfarin therapy to prevent cardiogenic cerebral embolism.

[Clinical features, neuroimaging and prognosis of adult patients with clinically diagnosed acute-onset encephalitis treated at a teaching neurology center in the Toyama area of Japan].

Although acute viral encephalitis (AVE) and acute disseminated encephalomyelitis (ADEM) are etiologically and pathologically distinct, a differential diagnosis between these two disorders is often difficult, especially if the patient exhibits a disturbance in consciousness. To identify useful clinical differences enabling a differential diagnosis to be made at an early stage, we retrospectively analyzed patients who had been admitted to our hospital within the past seven years because of acute-onset encephalitis with a disturbance in consciousness. Eleven adult patients were classified as having AVE, and 8 adult patients were classified as having ADEM within this period. The clinical characteristics of the two groups were then compared. Patients with AVE exhibited a disturbance in consciousness as their first neurological sign, whereas patients with ADEM initially showed focal signs like spastic paralysis, urinary disturbance and ataxia, which were followed by a disturbance in consciousness. ADEM is usually preceded by infection or vaccination, but obtaining a medical history from patients with disturbed consciousness is often difficult Based on the present analysis, the initial manifestation of focal neurological signs may be very useful for distinguishing ADEM from AVE.

[A case of Good syndrome accompanied by myasthenia gravis: immunological evaluations].

Good syndrome, characterized by both thymoma and hypogammaglobulinemia, is a rare immunodeficient disorder. We experienced a case of Good syndrome accompanied by myasthenia gravis (MG). A 58-year-old man was admitted to our hospital because of muscle weakness and fatigability. Based on the presence of anti-acetylcholine receptor (AChR) antibody and thymoma, he was diagnosed as having MG. Peripheral blood lymphocyte count was normal, but gammaglobulin levels were markedly decreased (IgG 283 mg/dl, IgA 17 mg/dl, IgM 1 mg/dl). Clinical remission of MG was achieved by thymectomy followed by high-dose corticosteroids. Despite monthly intravenous immunoglobulin supplementation, he suffered from repeated respiratory tract infections and candidiasis. Body CT revealed adrenal tumor and pancreatic cancer with liver metastasis, and he died of bacterial pneumonia. Immunological evaluations showed complete lack of CD19+ B cell in the peripheral blood and responses of peripheral blood mononuclear cells to mitogens. Peripheral blood T cells responded to a suboptimal concentration of a recombinant AChR fragment: this pattern of AChR-induced T cell response was typical of MG patients. We failed to detect IgG autoantibodies reactive with B cells in his serum. Patients with Good syndrome represent imbalance of immune responses, leading to both immunodeficiency and autoimmunity.