Schizophrenia following new-onset refractory status epilepticus secondary to antiphospholipid syndrome

New-onset refractory status epilepticus (NORSE) is a drug-resistant status epilepticus that often has a catastrophic outcome. Our patient was diagnosed with NORSE and had an EEG reading that showed status epilepticus persisting for 8 months in general anesthesia. After autoimmune workup showed positive antiphospholipid antibodies, his seizure was controlled, and he was discharged with good condition apart from moderate cognitive impairment. However, he later developed schizophrenia. Although psychiatric disorders have been associated with antiphospholipid syndrome, to the best of our knowledge, it has not been reported to be associated with status epilepticus. We recommend vigilance of psychological complications of refractory status epilepticus’ patients for early psychiatric referral, diagnosis, and treatment.

New-onset refractory status epilepticus (NORSE) is a syndrome of new-onset drug-resistant status epilepticus that often has a catastrophic outcome. Epilepsy is usually associated with psychiatric disorders of different manifestations of which psychosis is an example.1 However, not much is found in the literature review regarding psychiatric disorders following NORSE although a recent study concluded 32% of NORSE patients ended up with altered behavioral states like aggression.2 Schizophrenia following NORSE like in the rare presentation of this case has not been reported in the literature review before, although an association between schizophrenia and autoimmune disorders like APS has been reported.3     

Update Schütteltraumasyndrom

Monatsschrift Kinderheilkunde - Das Schütteltraumasyndrom (STS), im englischen Sprachgebrauch ?abusive head trauma“ (AHT), ist eine klar definierte und gängige medizinische...     

A comprehensive non‐invasive framework for automated evaluation of acute renal transplant rejection using DCE‐MRI

The objective was to develop a novel and automated comprehensive framework for the non‐invasive identification and classification of kidney non‐rejection and acute rejection transplants using 2D dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). The proposed approach consists of four steps. First, kidney objects are segmented from the surrounding structures with a geometric deformable model. Second, a non‐rigid registration approach is employed to account for any local kidney deformation. In the third step, the cortex of the kidney is extracted in order to determine dynamic agent delivery, since it is the cortex that is primarily affected by the perfusion deficits that underlie the pathophysiology of acute rejection. Finally, we use an analytical function‐based model to fit the dynamic contrast agent kinetic curves in order to determine possible rejection candidates. Five features that map the data from the original data space to the feature space are chosen with a k‐nearest‐neighbor (KNN) classifier to distinguish between acute rejection and non‐rejection transplants. Our study includes 50 transplant patients divided into two groups: 27 patients with stable kidney function and the remainder with impaired kidney function. All of the patients underwent DCE‐MRI, while the patients in the impaired group also underwent ultrasound‐guided fine needle biopsy. We extracted the kidney objects and the renal cortex from DCE‐MRI for accurate medical evaluation with an accuracy of 0.97 ± 0.02 and 0.90 ± 0.03, respectively, using the Dice similarity metric. In a cohort of 50 participants, our framework classified all cases correctly (100%) as rejection or non‐rejection transplant candidates, which is comparable to the gold standard of biopsy but without the associated deleterious side‐effects. Both the 95% confidence interval (CI) statistic and the receiver operating characteristic (ROC) analysis document the ability to separate rejection and non‐rejection groups. The average plateau (AP) signal magnitude and the gamma‐variate model functional parameter α have the best individual discriminating characteristics. Copyright © 2013 John Wiley & Sons, Ltd.     

Role of viral RNA and lipid in the adverse events associated with the 2010 Southern Hemisphere trivalent influenza vaccine

In Australia, during the 2010 Southern Hemisphere (SH) influenza season, there was an unexpected increase in post-marketing adverse event reports of febrile seizures (FS) in children under 5 years of age shortly after vaccination with the CSL 2010 SH trivalent influenza vaccine (CSL 2010 SH TIV) compared to previous CSL TIVs and other licensed 2010 SH TIVs. In an accompanying study, we described the contribution to these adverse events of the 2010 SH influenza strains as expressed in the CSL 2010 SH TIV using in vitro cytokine/chemokine secretion from whole blood cells and induction of NF-κB activation in HEK293 reporter cells. The aim of the present study was to identify the root cause components that elicited the elevated cytokine/chemokine and NF-κB signature. Our studies demonstrated that the pyrogenic signal was associated with a heat-labile, viral-derived component(s) in the CSL 2010 SH TIV. Further, it was found that viral lipid-mediated delivery of short, fragmented viral RNA was the key trigger for the increased cytokine/chemokine secretion and NF-κB activation. It is likely that the FS reported in children <5 years were due to a combination of the new influenza strains included in the 2010 SH TIV and the CSL standard method of manufacture preserving strain-specific viral components of the new influenza strains (particularly B/Brisbane/60/2008 and to a lesser extent H1N1 A/California/07/2009). These combined to heighten immune activation of innate immune cells, which in a small proportion of children <5 years of age is associated with the occurrence of FS. The data also demonstrates that CSL TIVs formulated with increased levels of splitting agent (TDOC) for the B/Brisbane/60/2008 strain can attenuate the pro-inflammatory signals in vitro, identifying a potential path forward for generating a CSL TIV indicated for use in children <5 years.     

Estratificación basal de riesgo en pacientes mayores de 75 años con infarto y shock cardiogénico referidos para angioplastia primaria

Background and objectivesPatients older than 75 years with ST-segment elevation myocardial infarction undergoing primary angioplasty in cardiogenic shock have high mortality. Identification of preprocedural predictors of short- and long-term mortality could be useful to guide decision-making and further interventions.MethodsWe analyzed a nationwide registry of primary angioplasty in the elderly (ESTROFA MI + 75) comprising 3576 patients. The characteristics and outcomes of the subgroup of patients in cardiogenic shock were analyzed to identify associated factors and prognostic predictors in order to derive a baseline risk prediction score for 1-year mortality. The score was validated in an independent cohort.ResultsA total of 332 patients were included. Baseline independent predictors of mortality were anterior myocardial infarction (HR 2.8, 95%CI, 1.4-6.0; P = .005), ejection fraction < 40% (HR 2.3, 95%CI, 1.14-4.50; P = .018), and time from symptom onset to angioplasty > 6 hours (HR 3.2, 95%CI, 1.6-7.5; P = .001). A score was designed that included these predictive factors (score “6-ANT-40”). Survival at 1 year was 54.5% for patients with score 0, 32.3% for score 1, 27.4% for score 2 and 17% for score 3 (P = .004, c-statistic 0.70). The score was validated in an independent cohort of 124 patients, showing 1-year survival rates of 64.5%, 40.0%, 28.9%, and 22.2%, respectively (P = .008, c-statistic 0.68).ConclusionsA preprocedural score based on 3 simple clinical variables (anterior location, ejection fraction < 40%, and delay time > 6 hours) may be used to estimate survival after primary angioplasty in elderly patients with cardiogenic shock and to guide preinterventional decision-making.     

A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent,persistent or metastatic cervical cancer

Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m² as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m²) or cisplatin (50 mg/m²) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5–96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.     

Developing fMRI protocol for clinical use Comparison of 6 Arabic paradigms for brain language mapping in native Arabic speakers

Objectives:To assess a baseline assessment using developed functional magnetic resonance imaging (fMRI) language paradigms for Arabic-speakers.Methods:24-healthy right-handed volunteers scanned on a 3.0 Tesla MRI machine. For fMRI, a BOLD-sensitive sequence used to measure signals over time across 6 language paradigms: rhyming (RH), semantic category generations (SCG), silent word generation (SWG), verb generation picture (VGp), verb generation word (VGw), and verb generation audio (VGa). fMRI data was analyzed using FMRIB Software Library (FSL).Results:We found that VGa, SWG, VGw and VGp robustly activated language-related regions in the dominant hemisphere. RH and SCG failed to adequately define these activation regions but this may be related to the study’s preliminary nature and limitations. After assessment of their validity, considerable activation of the inferior frontal gyrus during VGa, SWG, VGw and VGp suggests that these paradigms have the potential for localizing of Broca’s area in native Arabic speakers.Conclusion:Set of well adapted, and evidence-based, fMRI paradigms were established for Arabic-speakers to enable accurate and sufficient localization and lateralization of the language area. After validation, these paradigms may provide sequences for accurate localization of brain language areas, and could be used as a presurgical evaluation tool.

Functional magnetic resonance imaging (fMRI) allows precise, and non-invasive, localization and lateralization of brain functions. Clinically, these techniques have considerable success, and hold great potential in the management of a variety of neurological disorders. One of the most promising clinical applications of fMRI is presurgical linguistic mapping.1-5 The 3 classical language areas that are involved in language production and processing are Broca’s and Wernicke’s areas, and angular gyrus. Wernicke’s area can be described as a receptive region, for processing and integrating auditory sensory information, while Broca’s area can be described as a productive region, for making vocal signals, and meaningful words or sentences. The latter includes pars opercularis and triangularis. The angular gyrus area is particularly involved in reading and transitioning between written and spoken forms of language. Injury to language regions produces noticeable clinical deficits, and the location of these regions may become difficult to assess without advanced anatomical imaging such as fMRI. Internationally, fMRI replaces the more invasive Wada test (also known as the intracarotid sodium amobarbital procedure) in lateralizing language and memory at some centers.6,7Language is a highly complex system that markedly varies across individuals. Patients native language affects brain activation responses during fMRI scans.8-13 As such, language paradigms for presurgical fMRI mapping should be developed and validated using native language paradigms. Language dominance of the left cerebral hemisphere has been well researched and established, but native language and social factors were also reported to play a key role in cortical association of verbal processing.8,14-16Although language localization using fMRI has been routinely used in western countries, and more recently in an Arabic country,17 studies clearly demonstrated that different cultures may process language in different manners, using different brain mechanisms.8,14-16 Existing language paradigms, created for non-Arabic speaking patients, require major modifications before applying them in examining native Arabic speakers.17Language lateralization is another broadly used clinical application of fMRI. Concordance with Wada test has long been demonstrated and validated in the literature using paradigms with various tasks such as verbal fluency, comprehension, and semantic judgment .18-21 These have shown that concordance with Wada test can reach 90% in temporal lobe epilepsy, especially in left-dominant patients. A slightly lower concordance was achieved in right-dominant patients. Although fMRI language lateralization works well for patients with typical language dominance, clinicians need to be careful when interpreting results of patients with atypical language representation.22Semitic languages such as Arabic differ from other languages in many aspects, including orthography (including diacritics), phonology, and syntax. Therefore, significant research in developing and validating language paradigms for Arabic is required. To our knowledge, very few studies in this domain have been carried out.17,23 One developed several language and memory paradigms in neurological patients, while emphasizing consideration for educational and cultural adjustments,17 and the other examined neuronal correlates of diacritics (vs. lack of thereof) in 11 healthy men.23We aim to establish tasks adapted to the Arabic language, that also reliably activate Broca’s and Wernicke’s areas in a relatively short scanning time. This study is a baseline assessment using 6 developed fMRI language paradigms for Arabic-speaking presurgical candidates. The desired outcome of this work is to create a set of Arabic language localization protocols, along with standard operating procedures.     

Impact of body weight on long-term survival after lung transplantation

STUDY OBJECTIVES: The purpose of this study was to determine the impact of a pretransplantation determination of body mass index (BMI) on survival after lung transplantation. DESIGN AND PATIENTS: Univariate and multivariate survival analyses of a single institution database consisting of 85 patients who had undergone lung transplantations between March 1994 and October 1998. SETTING: University of Florida Health Science Center. RESULTS: Kaplan-Meier survival curves showed that patients who were obese (ie, BMI, > or = 30) at a pretransplantation assessment had a marked decrease in posttransplantation survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression model revealed that the most powerful predictors of mortality after lung transplantation were higher pretransplantation BMI and the development of obliterative bronchiolitis. CONCLUSIONS: Our results suggest that the posttransplantation risk for mortality is possibly three times greater for obese patients than for nonobese patients. Additional study is needed to identify the mechanisms for such higher risk in obese patients. Our data also suggest that transplantation centers should not routinely reject underweight patients (ie, BMI, < 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung transplantation listing solely on the basis of weight, as their outcomes may not be significantly different than patients with normal BMIs.