Nonconvulsive Status Epilepticus Caused by Cerebrospinal Fluid Dissemination of a Salivary Duct Carcinoma: A Case Report.

Salivary duct carcinoma (SDC) is a rare and highly aggressive salivary gland tumor with rapid growth, distant metastasis, and a high recurrence rate. Moreover, the parotid gland is the most common site with a poor prognosis. A lower frequency of distance metastasis to the liver, skin, and brain has also been reported, although the lungs, bones, and lymph nodes are the most common sites of SDC metastasis. We report a case of nonconvulsive status epilepticus (NCSE) in a 73-year-old male comatose patient having SDC of the parotid gland with an unusual metastasis to the skin and brain diagnosed by frequent cerebrospinal fluid examinations. Meningeal carcinomatosis usually has a poor prognosis, and NCSE is a reversible cause of altered mentation. Clinicians should know the unique set of epilepsy etiologies in patients with malignant tumors.

Psychiatric disorders of the combination of levetiracetam either with lacosamide or perampanel: a retrospective cohort study.

Background The number of patients with epilepsy receiving perampanel or lacosamide as an add-on treatment following levetiracetam treatment has increased. Although levetiracetam causes psychiatric disorders, it is unclear whether they occur with the combined use of these antiepileptic drugs. Objective To determine the frequency of psychiatric disorders in patients received lacosamide or perampanel in combination with levetiracetam. Setting A single-center retrospective cohort study. Method Patients who received levetiracetam + lacosamide or levetiracetam + perampanel were selected. Medical records from the start of combination therapy contained characteristics of patients and the incidence of psychiatric disorders. Main outcome measure The frequency of psychiatric disorders, the time to onset, dose reduction or discontinuation following psychiatric disorders, and the clinical course following disorder onset. Results Forty-four patients used levetiracetam + lacosamide and 50 used levetiracetam + perampanel. The incidence of psychiatric disorders was significantly lower (p < 0.001) with levetiracetam + lacosamide (6.8%) than with levetiracetam + perampanel (44%). The incidence of affect lability was significantly higher with levetiracetam + perampanel than with levetiracetam + lacosamide (p = 0.018). The time to the onset of psychiatric disorders was within 1 month of dose initiation or increase in one case (33.3%) with levetiracetam + lacosamide and 16 cases (72.7%) with levetiracetam + perampanel. There was no significant difference in clinical characteristics and antiepileptic drug dosages owing to the presence or absence of psychiatric disorders. Conclusion As the frequency of psychiatric disorders was higher with levetiracetam + perampanel therapy, levetiracetam + lacosamide may be preferable. These disorders tended to develop within 1 month of therapy and were not dose-dependent. Antiepileptic drugs should be cautiously prescribed to avoid psychiatric disorders.

First Report of Fatal Infection Caused by Community-acquired Methicillin-resistant Staphylococcus aureus USA300 Clone in a Collegiate Athlete.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is prevalent around the world and is a causative agent of skin and soft tissue infections in healthy individuals. Particularly, Panton-Valentine leukocidin (PVL)-positive CA-MRSA strains occasionally cause life-threatening infections, such as septic pulmonary emboli (SPE) and infectious endocarditis. However, severe infections caused by PVL-positive CA-MRSA strains have rarely been reported in Japan. For the first time, this study reports the case of a 20-year-old Japanese college athlete with life-threatening PVL-positive CA-MRSA USA300 clone infection, including sepsis, SPE, and skin and soft tissue infections with iliofemoral deep venous thrombosis.

A risk as an infection route: Nasal colonization of methicillin-resistant Staphylococcus aureus USA300 clone among contact sport athletes in Japan.

Panton-Valentine leukocidin (PVL)-positive USA300 clone is a highly pathogenic and global epidemic community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) clone. Athletes are particularly vulnerable to CA-MRSA infection because of the frequency of skin trauma, close-contact situations, and sharing of equipment that is customary in the athletic setting. We experienced a case of Japanese collegiate football player with septic pulmonary emboli secondary to infectious iliofemoral deep venous thrombosis caused by the USA300 clone. Here, we screened the nasal carriage of USA300 clone colonization among asymptomatic teammate of the patient to elucidate the infection route. Among 69 nasal samples, CA-MRSA strains were found in 5.8% (four samples). Molecular epidemiological analyses showed that three of the CA-MRSA strains were USA300 clone. Furthermore, pulsed-field gel electrophoresis revealed that all nasal USA300 clones showed 100% identity with the USA300 clone isolated from their teammate with critical infection. Our findings indicate that nasal colonization of the PVL-positive CA-MRSA, especially USA300 clone, pose a threat among contact sport athletes in Japan likewise other countries. An immediate infection control strategy for contact sport athletes is necessary to prevent outbreaks of PVL-positive CA-MRSA infections.

Endogenous genetic risk factor for serious heatstroke: the thermolabile phenotype of carnitine palmitoyltransferase II variant.

AIM: In serious heatstroke, elevated body temperature (>40°C) is considered the main cause of illness. Mitochondrial carnitine palmitoyltransferase II (CPT II) plays an important role in adenosine triphosphate (ATP) generation from long-chain fatty acids, and its thermolabile phenotype of CPT2 polymorphisms leads to ATP production loss under high fever. Whether by heatstroke or influenza, high fever suppresses mitochondrial ATP production in patients with the thermolabile phenotype of CPT2 polymorphisms. We investigated the relation between CPT2 polymorphism and severity of heatstroke with a body temperature of over 40°C. METHODS: We analyzed blood chemistry test results, Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC), Acute Physiologic and Chronic Health Evaluation II, and Sequential Organ Failure Assessment (SOFA) scores, and CPT2 polymorphisms in 24 consecutive patients with severe heatstroke at two university hospitals. RESULTS: Eleven patients carried thermolabile CPT II variants (rs2229291; c.1055T˃G [p.Phe352Cys]) (F352C), and the genotype frequency was greater in heatstroke patients than in healthy volunteers. There was no significant difference in body temperature or blood chemistry data at emergency room arrival between patients with and without the CPT II variants. However, hospital days were longer and initial antithrombin activity was significantly lower in the variant group, suggesting a possible link with early phase vascular endothelial cell dysfunction. The JAAM DIC diagnostic criteria and SOFA scores were also higher in the group. There were no differences in the serum albumin, serum creatine kinase, and fibrin degradation product levels, and platelet counts. CONCLUSIONS: In addition to known risks (e.g., environmental temperature and old age), the CPT II polymorphism [F352C] can be a predisposing genetic risk factor for serious heatstroke with organ disfunction, and lower antithrombin activity.

Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder Treated With Antithrombin Supplementation.

For success in clinical trials, eliminating inclusion of patients with irreversible recovery is important. The purpose of this study was to identify the patient population who do not survive for more than 3 days. A total of 449 patients with sepsis suspected of having disseminated intravascular coagulation (DIC) and treated with antithrombin were examined. The patient characteristics, baseline sequential organ failure assessment (SOFA) score, DIC score, and hemostatic markers were retrospectively analyzed in relation to early death (died within 3 days). At the end of day 3, a total of 419 patients had survived and 30 patients had died. A logistic regression analysis revealed a significant association between early death and the baseline prothrombin time-international normalized ratio PT-INR (P <.05) and the total SOFA score (P <.01). In contrast, neither the platelet count, fibrinogen/fibrin degradation products, and antithrombin activity nor the DIC score was associated with early death. Although the accuracy for predicting early death defined by either baseline PT-INR of ≥1.57 or total SOFA score of more than 13 was not high enough, that of "high-risk of early death (PT-INR ≥ 1.57 and SOFA score ≥ 13)" was 83.5%. Furthermore, the negative predictive of this category was 96.0%. The baseline SOFA score and PT-INR were associated with early death among patients with sepsis-associated coagulation disorders. Patients who do not meet the "high-risk of early death" criteria were likely to survive for more than 3 days and therefore should be considered for future therapeutic clinical trials.

Empirical research on the utility of a preparation manual for a disaster medical response drill.

PURPOSE: It is difficult for emergency physicians to plan and execute a disaster medical response drill while conducting their daily work activities. Readily available drill preparation manuals are therefore essential, alongside assessment methods to ensure quality. Here, we propose email text analysis as a manual assessment method, and investigate its validity. METHODS: The preparation status of two similar large-scale disaster medical response drills were compared. All email texts exchanged during the preparation stage were analyzed, and frequently appearing words (quality element) and word counts (quantity element) were compared between Drill 1, which was organized without a manual, and Drill 2, organized with a manual. RESULTS: Word frequency analysis revealed that the key components of the manual (visualization of necessary work, preparation of documents in a certain format, and clarification of aims of the drill) contributed to the effectiveness of the preparation process for Drill 2. Furthermore, work volume during the preparation for Drill 2 was decreased by 41.9% from that during the preparation for Drill 1. CONCLUSION: Preparation of a high-quality manual is crucial so that emergency physicians can plan and execute a disaster medical response drill. Email text analysis can serve as an objective method assessing the quality of manuals.

[A Case of Amusia Following Right Temporal Subcortical Hemorrhage].

A woman in her 60s presented with amusia due to a localized subcortical hemorrhage of the right temporal lobe. No other symptoms of higher brain dysfunction or body paralysis were observed. One characteristic symptom in this case was rhythm impairment. Few cases of this impairment have been previously reported, and the responsible lesion and underlying mechanisms are still a matter of speculation. However, in this case, a relationship with the right temporal lobe was indicated.

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma.

BACKGROUND: This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region. Toxicity, progression-free survival (PFS), and overall survival (OS) of this trial were evaluated. Expressions of WT-1, gp-100, and MAGE-A3, recognized as chemoresistance-associated peptides (CAP), were confirmed by immunohistochemistry of paraffin-embedded tumor samples. Patient's PBMCs of pre- and post-vaccination were evaluated by tetramer and ELISPOT assays. RESULTS: FC-immunotherapy was well tolerated in all patients. Medians of PFS and OS of Group-R (n = 10) were 10.3 and 18.0 months, and those of Group-N (n = 22) were 18.3 and 30.5 months, respectively. Up-regulation and/or cytoplasmic accumulation of CAPs was observed in the recurrent tumors of Group-R patients compared with their initially excised tumors. Specific immune responses against CAPs were observed in the tetramer and ELISPOT assays. CONCLUSIONS: The combination of TMZ-treatment leading to up-regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a means of producing specific immunity against CAPs, may safely induce anti-tumor effects in patients with GBM.

Procalcitonin levels predict to identify bacterial strains in blood cultures of septic patients.

BACKGROUND: We examined whether the values obtained from principal component analysis (PCA) on laboratory tests can be used to predict bacterial infections and identify bacterial strains in blood culture (BC). METHOD: This study is a single-center retrospective analysis of 315 patients suspected of having sepsis. We applied PCA on procalcitonin (PCT) and laboratory test biomarkers, namely, platelet (PLT), white blood cell, and C-reactive protein (CRP) as well as BC. RESULTS: Principal component analysis showed that PCT, CRP, and PLT contributions to component 1 were associated with bacterial infection. The number of patients who had BC-negative results, gram-positive cocci (GPC), and gram-negative rods (GNRs) were 124, 28, and 19, respectively. The mean value of component 1 in GNR-positive patients was 1.58±1.41 and was significantly higher than that in GPC-positive patients (0.28±0.87; P<.0001). Furthermore, the mean values of component 1 in both GNR- and GPC-positive patients were significantly higher than that in BC-negative patients (-0.31±0.65; P<.0001 and P<.002, respectively). One certain range showing higher value more than 2.00 for component 1 and -1.00 for component 2 only included GNR-positive patients. There were no BC-positive patients who showed less than -1.00 for component 1. CONCLUSION: The present results obtained by PCA on laboratory tests involving PCT, PLT, white blood cell, and CRP suggest the potential of PCA-obtained values to not only predict bloodstream infection but also identify bacterial strains. This provides some clinical significance in the management of sepsis in acute care.

[Burns].

Burns extending deep into the skin and those affecting a wide surface area trigger various responses in the body and pose a serious threat to life. Therefore, the degree of severity needs to be determined accurately, and appropriate transfusion and local management should be provided accordingly. Systematic and meticulous management that considers not just the risk of death but also functional prognosis is essential from the early stage of burn injuries. Such management requires comprehensive care by a medical team concerning infections, nutrition and rehabilitation. This article outlines the current status of intensive care for severe burns.

Investigation and treatment of pulmonary embolism as a potential etiology may be important to improve post-resuscitation prognosis in non-shockable out-of-hospital cardiopulmonary arrest: report on an analysis of the SOS-KANTO 2012 study.

Background: The prognosis of non-shockable out-of-hospital cardiac arrest is worse than that of shockable out-of-hospital cardiac arrest. We investigated the associations between the etiology and prognosis of non-shockable out-of-hospital cardiac arrest patients who experienced the return of spontaneous circulation after arriving at hospital. Methods and Results: All subjects were extracted from the SOS-KANTO 2012 study population. The subjects were 3,031 adults: (i) who had suffered out-of-hospital cardiac arrest, (ii) for whom there were no pre-hospital data on ventricular fibrillation/pulseless ventricular tachycardia until arrival at hospital, (iii) who experienced the return of spontaneous circulation after arriving at hospital. We compared the patients' prognosis after 1 and 3 months between various etiological and presumed cardiac factors. The proportion of the favorable brain function patients that developed pulmonary embolism or incidental hypothermia was significantly higher than that of the patients with presumed cardiac factors (1 month, P < 0.0001 and P < 0.0001, respectively; 3 months, P = 0.0018 and P < 0.0001, respectively). In multiple logistic regression analysis, pulmonary embolism and incidental hypothermia were found to be significant independent prognostic factors for 1- and 3-month survival and the favorable brain function rate. Conclusions: In patients who suffer non-shockable out-of-hospital cardiac arrest, but who experience the return of spontaneous circulation after arriving at hospital, the investigation and treatment of pulmonary embolism as a potential etiology may be important for improving post-resuscitation prognosis.

[A Case of Foix-Alajouanine Syndrome due to Perimedullary AVF: Remission and Aggravation Mechanism Considered by an Open Surgical Biopsy and Intraoperative ICG Angiography].

Foix-Alajouanine syndrome (FAS), also known as congestive myelopathy due to spinal vascular malformations, presents with paraplegia, sensory disturbance of lower limbs, and dysfunction of the bladder and rectum. Although FAS is characterized by a subacute onset of neurological symptoms that may wax and wane over a few years, the progression mechanism remains unclear. We report a case of FAS due to an angiographically occult arteriovenous fistula (AVF) that was diagnosed by an open surgical biopsy and intraoperative indocyanine green (ICG) angiography. The patient was a 74-year-old female who presented with a one-year history of gradually progressive gait disturbance, weakness, and decreased sensation in her legs associated with bladder and rectum dysfunction. MRI showed intramedullary T1 hypointensity, T2 hyperintensity at level Th4-12, and intramedullary enhancing with a Gd-DTPA lesion at level Th8-12. A true-FISP image of the MRI revealed an abnormal tortuous vessel in the dorsal spinal subarachnoid space, but digital subtraction angiography of the spine at the C1-L5 level showed no abnormality. The patient also underwent Th8-12 laminectomy for open biopsy. ICG angiography revealed blood flow stagnation in an abnormally enlarged posterior spinal vein. Histological findings indicated necrotizing myelopathy and stenosis with wall thickening of the posterior spinal vein. We hypothesized that the progression mechanism in the present case may have resulted from histological changes in the draining veins of an AVF. Intraoperative ICG angiography may be a valuable method, not only for diagnosing AVFs but also for determining the existence and pathological characteristics of FAS.

Anti-NMDAR encephalitis: case report and diagnostic issues.

Case: A 20-year-old woman developed acute psychotic symptoms and altered level of consciousness. She presented with neck stiffness, tremulous arms, facial dyskinesia, and distension of the lower abdomen. Pelvic magnetic resonance imaging showed bilateral ovarian teratomas. Anti-N-methyl-D-aspartate receptor antibodies were detected in her cerebrospinal fluid. Outcome: Resection of the tumors and immunotherapy were carried out. She gradually recovered and was discharged with few neurological deficits on the 105th day of hospitalization. Conclusion: Our survey of 63 previous reports describing 92 cases revealed that 21.7% of the patients were sent to emergency departments and 59.8% of the patients were managed in intensive care units. Emergency physicians and intensivists should be aware of this disorder, as they may encounter undiagnosed disorders in patients with epileptic attacks, acute psychotic signs, dyskinesia, or hypoventilation in the course of the illness.

[Transient charles bonnet syndrome after excision of a right occipital meningioma: a case report].

Charles Bonnet syndrome is a condition characterized by visual hallucinations. These simple or complex visual hallucinations are more common in elderly individuals with impaired peripheral vision. The current report describes a case of transient Charles Bonnet syndrome appearing after the removal of a meningioma. The patient was a 61-year-old man who already had impaired visual acuity due to diabetic retinopathy. Brain MRI revealed a cystic tumor severely compressing the right occipital lobe. Starting on day 2 postoperatively, the patient was troubled by recurring visual hallucinations involving people, flowers, pictures, and familiar settings(the train and a coffee shop). These continued for 3.5 months. This period roughly coincided with the time for the occipital lobe to recover from the compression caused by the tumor, a fact that was confirmed by several MRI scans. ¹²³I-IMP SPECT performed 1 month after the surgical operation showed an area of hypoperfusion in the right parieto-occipital lobe. Based on the patient's clinical course and MRI findings, the mechanism of onset of visual hallucinations in this patient was put forward. The release of pressure in the brain by tumor removal and subsequent recovery changed the blood flow to the brain. This triggered visual hallucinations in the patient, who was already predisposed to developing Charles Bonnet syndrome because of diabetic retinopathy. This case is interesting since it indicates that central neurological factors, as well as visual deficits, may induce the appearance of visual hallucinations in Charles Bonnet syndrome.

Prediction of blood culture results by measuring procalcitonin levels and other inflammatory biomarkers.

BACKGROUND: It would be helpful if we could predict positive or negative blood culture results. This study considered the usefulness of measuring procalcitonin (PCT) level and standard clinical biomarkers such as white blood cell (WBC) count, C-reactive protein (CRP) level, and platelet (PLT) count to predict blood culture results. METHOD: We retrospectively analyzed the data from 422 specimens collected at our emergency center within the preceding 36 consecutive months. Primary component analysis (PCA) was used for detecting the degree of the relational contribution of each of the 4 biomarkers to the blood culture results. RESULTS: Procalcitonin alone (cut-off value, 0.5 ng/mL) yielded a positive blood culture rate of 34.0%. Procalcitonin plus 3 biomarkers (WBC, CRP, and PLT) analyzed by PCA yielded 45.9% or 35.3% when a case was in the first or fourth quadrant, which was significantly higher than cases in the second or third quadrant. Primary component analysis also revealed that positive blood culture results were mainly affected by primary component 1, to which PCT and PLT (not WBC or CRP) predominantly contribute. CONCLUSION: Although it is difficult to predict blood culture results, even using 4 biomarkers analyzed by PCA, our new finding that blood culture results are affected not by WBC and CRP, but mainly by PCT and PLT, might help explain the mechanism of sepsis.

Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer's disease brain.

BACKGROUND: Intracytoplasmic inclusions composed of filamentous tau proteins are defining characteristics of neurodegenerative tauopathies, but it remains unclear why different tau isoforms accumulate in different diseases and how they induce abnormal filamentous structures and pathologies. Two tau isoform-specific antibodies, RD3 and RD4, are widely used for immunohistochemical and biochemical studies of tau species in diseased brains. RESULTS: Here, we show that extensive irreversible post-translational deamidation takes place at asparagine residue 279 (N279) in the RD4 epitope of tau in Alzheimer's disease (AD), but not corticobasal degeneration (CBD) or progressive supranuclear palsy (PSP), and this modification abrogates the immunoreactivity to RD4. An antiserum raised against deamidated RD4 peptide specifically recognized 4R tau isoforms, regardless of deamidation, and strongly stained tau in AD brain. We also found that mutant tau with N279D substitution showed reduced ability to bind to microtubules and to promote microtubule assembly. CONCLUSION: The biochemical and structural differences of tau in AD from that in 4R tauopathies found in this study may therefore have implications for prion-like propagation of tau.

Long-term follow-up of growth hormone-producing pituitary carcinoma with multiple spinal metastases following multiple surgeries: case report.

This report describes a rare case of a patient with growth hormone (GH)-secreting pituitary adenoma with malignant transformation resulting in multiple metastases to the dura mater of the cerebral convexity and high cervical spine. The patient was a 60-year-old man with a previous history of pituitary adenoma with suprasellar extension who had undergone transsphenoidal surgery, craniotomy for a convexity tumor, and suboccipital craniotomy for a cerebellar tumor. Thirteen years after the initial surgery, suboccipital craniotomy for a cervicomedullary junction tumor and cervicospinal surgery for a metastatic tumor was performed. Histologic findings of resected specimens demonstrated that the primary pituitary tumor was typical adenoma (similar to specimens from the initial surgery) but that the cerebellar and the dural tumor from the high cervical spine had a high incidence of mitotic figures, and cellular anaplasia with nuclear polymorphism and necrosis. In addition, the serum levels of GH were noted to have decreased with recurrence of the tumor. It was concluded that patients with pituitary adenoma, even when benign, must be carefully followed for signs of malignant transformation, and spinal or distant metastases.

Biosynthetic conclusions from the functional dissection of oxygenases for biosynthesis of actinorhodin and related Streptomyces antibiotics.

Actinorhodin (ACT) produced by Streptomyces coelicolor A3(2) belongs to the benzoisochromanequinone (BIQ) class of antibiotics. ActVA-ORF5, a flavin-dependent monooxygenase (FMO) essential for ACT biosynthesis, forms a two-component enzyme system in combination with a flavin:NADH oxidoreductase, ActVB. The genes for homologous two-component FMOs are found in the biosynthetic gene clusters for two other BIQs, granaticin (GRA) and medermycin (MED), and a closely related antibiotic, alnumycin (ALN). Our functional analysis of these FMOs (ActVA-ORF5, Gra-ORF21, Med-ORF7, and AlnT) in S. coelicolor unambiguously demonstrated that ActVA-ORF5 and Gra-ORF21 are bifunctional and capable of both p-quinone formation at C-6 in the central ring and C-8 hydroxylation in the lateral ring, whereas Med-ORF7 catalyzes only p-quinone formation. No p-quinone formation on a BIQ substrate was observed for AlnT, which is involved in lateral p-quinone formation in ALN.