Usefulness of carotid duplex ultrasonography in predicting residual large-vessel occlusions after intravenous recombinant tissue plasminogen activator therapy in patients with acute ischemic stroke.

PURPOSE: Endovascular therapy (EVT) preceded by intravenous thrombolysis with recombinant tissue plasminogen activator (iv-rtPA) has been established as a standard treatment in patients with stroke caused by large-vessel occlusion (LVO). Primary stroke centers without EVT competence need to identify patients with residual LVO after iv-rtPA therapy and transport them to an EVT-capable facility. Carotid ultrasonography (CUS) is easily applicable at bed side and useful for detecting extra- and intracranial LVO. This study aimed to determine whether CUS findings at admission are useful to predict patients with residual LVO after iv-rtPA. METHODS: Patients scheduled to undergo iv-rtPA for acute cerebral infarction were registered. Before iv-rtPA, they underwent CUS, followed by CTA or MRA evaluation within 6 h after iv-rtPA. A model that can achieve 100% sensitivity for detecting residual LVO after iv-rtPA was studied. RESULTS: This study included 68 of 116 patients treated with iv-rtPA during the study period. National Institutes of Health Stroke Scale (NIHSS) score (cutoff value = 10) on arrival, hyperdense MCA sign on non-contrast CT, end-diastolic (ED) ratio on CUS, and eye deviation were significantly different between patients with residual LVO after iv-rtPA and those without. If any of these clinical features are positive in the screening test, residual LVO could be predicted with 100% sensitivity, 50% specificity, 64% positive predictive value, and 100% negative predictive value. CONCLUSION: Prediction of residual LVO with 100% sensitivity may be feasible by adding CUS to NIHSS score > 10, the presence of eye deviation, and hyperdense MCA sign.

Utility of transoral motion-mode ultrasonography to detect tongue fasciculation in patients with amyotrophic lateral sclerosis.

INTRODUCTION: Increasing evidence suggests the utility of the submandibular approach for ultrasonography to detect tongue fasciculation in amyotrophic lateral sclerosis (ALS). We hypothesized that transoral motion-mode ultrasonography (TOMU) would be useful to detect tongue fasciculation in patients with ALS. METHODS: Patients with sporadic ALS showing clinically definite tongue fasciculation were enrolled, and the ultrasonography findings of patients' tongues on TOMU and ultrasonography by the conventional submandibular approach were analyzed. RESULTS: Six patients with clinically definite ALS were enrolled in this study. Although small, irregular muscle movements of 5 to 10 mm in amplitude and 0.1 to 0.2 second in duration were detected in all patients by TOMU, similar muscle movements were detected in only two of the six patients by the submandibular approach. DISCUSSION: TOMU appeared to be useful for detecting tongue fasciculation in ALS patients. Further study is needed to better determine its role as a diagnostic tool for ALS.

Usefulness of the combination of iodine-123-metaiodobenzylguanidine scintigraphy and iodine-123-ioflupane scintigraphy in new-onset Parkinson's disease.

OBJECTIVES: The aim of this study was to study the significance of combining iodine-123-cardiac metaiodobenzylguanidine scintigraphy (I-MIBG scintigraphy) and iodine-123-ioflupane (I-ioflupane) dopamine transporter scintigraphy (I-ioflupane scintigraphy) in patients suspected of having Parkinson's disease (PD). PATIENTS AND METHODS: We carried out a retrospective study from April 2014 to December 2015 in 48 patients suspected of having new-onset PD who underwent both I-MIBG and I-ioflupane scintigraphies within 3 months. Cases included 37 patients diagnosed as having PD. Controls included 11 patients who had never been diagnosed as having PD or other diseases showing parkinsonism. The cutoff for diagnosing PD was a heart to mediastinum ratio (H/M ratio) of less than or equal to 2.2 for I-MIBG scintigraphy in the delayed phase and a specific binding ratio (SBR) of less than or equal to 3.8 for I-ioflupane scintigraphy. The combined use of both scintigraphies was studied using the formula SBR×H/M ratio as a marker for the logistic regression model. RESULTS: Sixteen (33.3%) patients had SBR of greater than 3.8: eight with PD; eight were controls. Five of eight patients had an H/M ratio of less than or equal to 2.2 (62.5%) and had PD. In the receiver-operating characteristic analysis, the SBR×H/M ratio cutoff was 12.5, with an area under the curve of 0.844 (95% confidence interval: 0.619-1). In an age-adjusted regression analysis in patients with SBR of greater than 3.8, the SBR×H/M ratio was associated significantly with an odds ratio of 0.69 (95% confidence interval: 0.48-0.98, P=0.041). CONCLUSION: If SBR is greater than 3.8, the SBR×H/M ratio can help diagnose PD. The combined use of the two scintigraphies can improve the diagnosis of PD.

A case of cerebral infarction during a hemodialysis procedure successfully treated with recombinant tissue plasminogen activator.

Thrombolytic therapy is an effective treatment for acute ischemic stroke and provides benefits and improvements that lead to better neurological outcomes. However, thrombolytic therapy with recombinant tissue plasminogen activator (r-tPA) in hemodialysis (HD) patients is limited because HD patients have a higher risk of bleeding. We report a case of a 75-year-old HD patient who presented with sudden aphasia during HD treatment. She was brought to the hospital for treatment for infarction. Following thrombolytic therapy, we achieved re-opening without complications. To our knowledge, no report has been published describing the patients who had a stroke during a maintenance HD session and were treated with r-tPA successfully. Although the number of HD patients treated with r-tPA is small and requires further investigation, thrombolytic therapy can be an alternative option. After weighing the risks and benefits and assessing each patient carefully, the use of r-tPA should be considered, even in HD patients.

Familial Adult-Onset Alexander Disease with a Novel GFAP Mutation.

The patient was a 65-year-old woman who became gradually more prone to falling from age 30 and who was visiting the hospital on an outpatient basis following a diagnosis of multiple system atrophy, cerebellar type. While eating, she started choking as a result of aspiration and was transported to our hospital by ambulance. Head magnetic resonance imaging (MRI) revealed tadpole-like atrophy of the brainstem, i.e. marked atrophy of the medulla oblongata and cervical spinal cord with disproportionately slight atrophy of the pons. Her eldest son also had the same symptoms, suggesting Alexander disease. A search of the glial fibrillary acidic protein gene revealed the previously unreported mutation Y242N. The same MRI findings and genetic mutation were confirmed in her 38-year-old son. Adult onset Alexander disease is a rare condition with very few reported familial cases. We hereby report this case with a discussion of the literature.

[Feasibility Study for Storage and Re-Utilization of Circulating Tumor Cells (CTCs)].

BACKGROUND: In this era of precision medicine, monitoring patients requires not only real time but also longitudinal sequence of samples at various time points. Based on this background, we focused on conditioned circumstances on fixation and storage for re-utilization of CTCs. MATERIALS: Instead of actual CTCs, Cell line (H1975) derived from lung cancer was used because of their scarceness of CTCs. METHODS: These cells were put on a slide by using an auto-smear device. The slides were evaluated under various centrifuge forces, fixations for the following storages. RESULTS AND DISCUSSION: The study indicated that 800 rpm for 1 min centrifuge and fixation by 95% ETOH was excellent. Further at least 5 cells per 1 mL cell solution were required for the following procedures including Fluorescence in situ hybridization (FISH) analysis. This study provides insights of new platform for evaluation of CTCs not only real time but also longitudinal sequence at various time points.

Novel use for an EGFR mutation-specific antibody in discriminating lung adenocarcinoma from reactive pneumocyte hyperplasia.

AIMS: Pulmonary ground-glass nodules (GGNs) are frequently observed. Histopathologically, their presentation can indicate a wide range of disorders from an inflammatory process to malignancy. An accurate diagnosis based on GGNs can sometimes be challenging on small-sized biopsies. Mutations in the EGFR gene are detected in pulmonary adenocarcinomas (ADCs). Immunohistochemical analysis using antibodies that detect specific EGFR mutations has been shown to correlate with mutational status as determined by molecular methods. We hypothesized that these antibodies could be used to discriminate between ADCs and benign pneumocyte hyperplasias. METHODS AND RESULTS: Surgically resected, pre-invasive to invasive lung ADC (n = 32) and reactive pneumocyte hyperplasia (n = 40) tissue samples were probed with antibodies against EGFR mutations, p53, Mouse double minute 2 and 14-3-3 sigma. Of the 32 lung ADC specimens analysed, 12 (38%) were positive using the EGFR mutation-specific antibodies, while no immunoreactivity was observed in reactive pneumocyte hyperplasia specimens. Analyses of receiver operating characteristic curves showed that the highest area under the curve values were associated with the use of EGFR mutation-specific antibodies. In addition, a high concordance rate was observed between surgically resected and corresponding biopsy materials using these antibodies. CONCLUSIONS: EGFR mutation-specific antibodies can be used to discriminate between lung ADC and benign pneumocyte hyperplasia, even in small-sized biopsies.

Desmoplastic small round cell tumor with sphere-like clusters mimicking adenocarcinoma.

Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive neoplasm that predominantly affects young men. DSRCT often presents as multiple nodules on the serosal surface and is histologically categorized as a small round cell tumor. However, the cytological spectrum of DSRCT is not fully understood because of its rarity. Here, we report an unusual case of DSRCT that showed spheres of cells without stromal cores in pleural fluid cytology material, a finding that is typically associated with metastatic adenocarcinoma and mesothelioma. The specimen from a simultaneous needle biopsy showed the classic histology of DSRCT, comprising nests of small round cells set in desmoplasia. The diagnosis of DSRCT was further supported by immunohistochemical coexpression of cytokeratin and desmin, as well as Ewing sarcoma breakpoint region 1 gene rearrangement, which was determined by fluorescence in situ hybridization. The unusual cytological finding in this case illustrates a potential pitfall of the cytological diagnosis of pleural fluid or ascites. DSRCT should not be excluded from the differential diagnosis when sphere-like round cell clusters are observed in pleural or abdominal effusion, particularly in young male patients.

Impact of life and family background on delayed presentation to hospital in acute stroke.

The over-65 population stands at 29 million, more than 20% of the total population in Japan. This is the highest rate in the world. One-person households and older couple households will be increasing. The aim of the present study was to identify whether life and family background are significant factors for delayed presentation to hospital after stroke onset. A total of 253 patients (mean age, 70.7 ± 13.2 years) with stroke was examined. Patients who presented to hospital within 3 hours of onset were categorized as the early presentation group, and the other patients were categorized as the late presentation group. Life and family background were classified into 3 categories, namely 1-person households, 2-person households, and patients living with 3 or more persons. Two-person households were further subdivided by the age of family members. Multivariate logistic regression analysis demonstrated that 1-person households (odds ratio [OR]: 2.980, 95% confidence interval [CI]: 1.108-8.011) and 2-person households with individuals 65 years and older (OR: 3.059, 95% CI: 1.297-7.217) were significant independent factors for delayed presentation, in addition to stroke subtype, time of stroke onset, and route of admission. Onset-to-door time in patients with night-time onset was significantly different among different types of households. Significant delay was demonstrated in 2-person households with 2 individuals 65 years and older compared with that in patients living with 3 or more persons (P = .038). Our findings show that delayed presentation to hospital is more likely in stroke patients living in an elderly couple household, especially those with evening onset in an aging society.

A case of rhabdomyolysis in which levetiracetam was suspected as the cause.

Several studies have reported rhabdomyolysis induced by various drugs but not by the antiepileptic drug levetiracetam. We present a case of suspected levetiracetam-induced rhabdomyolysis. A 29-year-old woman was hospitalized for generalized tonic-clonic seizure and given levetiracetam for the first time. One day after starting levetiracetam, she developed myalgia, particularly backache, and weakness in both lower limbs. Based on her clinical symptoms and blood test results indicating hyperCKemia, our diagnosis was levetiracetam-induced rhabdomyolysis. Withdrawal of levetiracetam immediately improved the clinical symptoms and hyperCKemia. This first report of suspected levetiracetam-induced rhabdomyolysis provides important information for treating patients early in levetiracetam administration.

Pulmonary neuroendocrine tumors with nuclear inclusion.

Nuclear inclusion or pseudoinclusion is a peculiar cytological feature, and its recognition in appropriate clinicopathological settings can aid in the diagnosis of several disease entities. To the best of our knowledge, only 1 case of pulmonary neuroendocrine tumor (NET) with nuclear pseudoinclusion has been reported. A review of 227 patients who had undergone surgical resection for pulmonary NETs revealed 2 tumors with different mechanisms of nuclear inclusion. To explore the cause of nuclear inclusion, NET with nuclear inclusion was characterized immunohistochemically and ultrastructurally. Nuclear inclusions were observed in 2 of the 227 (0.9%) patients with pulmonary NETs. The first patient was a 46-year-old woman with small cell carcinoma. Tumor cells with nuclear inclusions were distributed focally. Ultrastructural analysis showed that these inclusions were pseudoinclusions. The second patient was a 62-year-old man with large-cell neuroendocrine carcinoma. Nuclear inclusions were observed in the focal area of the tumor. Immunohistochemical analysis revealed that the intra-nuclear materials consisted of biotin and aberrant cytoplasmic and nuclear accumulation of ß-catenin. Mutational analysis revealed a CTNNB1 gene mutation. Although very rare, diagnostic errors may be observed in cases of pulmonary NETs with nuclear inclusions. The mechanisms of nuclear inclusion differed, with one due to herniation of the cytoplasm into the nucleus (pseudoinclusion) and the other due to accumulation of biotin resulting from a CTNNB1 gene mutation.

Prediction of thrombolytic therapy after stroke-bypass transportation: the Maria Prehospital Stroke Scale score.

There is no prehospital stratification tool specifically for predicting thrombolytic therapy after transportation. We developed a new prehospital scale named the Maria Prehospital Stroke Scale (MPSS) by modifying the Cincinnati Prehospital Stroke Scale. Our objective is to evaluate its utility in a citywide bypass transportation protocol for intravenous (IV) tissue plasminogen activator (tPA). In the MPSS, facial droop, arm drift, and speech disturbance are tested by emergency medical technicians (EMTs). Facial droop is graded as normal (0) or abnormal (1), and the other 2 items are graded in 3 levels as normal (0), not severe (1), and severe (2). Thus, the total MPSS score ranges from 0 to 5. The predictive value of MPSS for thrombolytic therapy after bypass transportation was evaluated in 1057 patients. The MPSS scored by EMTs was significantly correlated with the National Institutes of Health Stroke Scale score in the emergency room (Spearman rho = .67, P = .000). The onset-to-door time was significantly longer with a low MPSS score (analysis of variance, F5,4.21 = .001). The rate of thrombolytic therapy was increased when the MPSS score increased from 0 to 5: 0%, 4.1%, 8.8%, 13.0%, 20.3%, and 31.5%, respectively. The areas under the receiver operating characteristic curve for the correct diagnosis of stroke and prediction of IV tPA therapy were calculated as .737 (95% confidence interval [CI]: .688-.786) and .689 (95% CI: .645-.732), respectively. Multivariate logistic regression analysis showed that the MPSS score and the detection-to-door time were independent predictors of tPA use after transportation. The MPSS is a novel prehospital stratification tool for the prediction of thrombolytic therapy after transportation.