Project description:Ictal asystole is a rare, serious, and often treatable cause of syncope. There are currently limited data to guide management. Characterization of ictal syncope predictors may aid in the selection of high-risk patients for treatments such as pacemakers.We searched our epilepsy monitoring unit database from October 2003 to July 2013 for all patients with ictal asystole events. Clinical, electroencephalogram, and ECG data for each of their seizures were examined for their relationships with ictal syncope events. In 10 patients with ictal asystole, we observed 76 clinical seizures with 26 ictal asystole episodes, 15 of which led to syncope. No seizure with asystole duration?6 s led to syncope, whereas 94% (15/16) of seizures with asystole duration>6 s led to syncope (P=0.02). During ictal asystole events, 4 patients had left temporal seizure onset, 4 patients had right temporal seizure onset, and 2 patients had both. Syncope was more common with left temporal (40%) than with right temporal seizures (10%; P=0.002). Treatment options included antiepileptic drug changes, epilepsy surgery, and pacemaker implantation. Eight patients received pacemakers. During follow-up of 72±95 months, all patients remained syncope free.Ictal asystole>6 s is strongly associated with ictal syncope. Ictal syncope is more common in left than in right temporal seizures. A permanent pacemaker should be considered in patients with ictal syncope if they are not considered good candidates for epilepsy surgery.
Project description:We present the case of a patient with syncope with repetition over 12 years, with a clinical profile not clearly related with a cardiogenic origin, who was studied by several medical specialties without any accurate diagnosis. After subcutaneous loop recorder implantation, we were able to demonstrate how seizures acted as a trigger in the genesis of an exaggerated cardio inhibitory reflex. A new entity has been described, known as "ictal asystole", in patients with focal epilepsy mostly from the temporal lobes and has been implicated as a cardiac cause of sudden unexplained death in epilepsy. We think this case could add new information about some patients who are at high risk of death but they are misdiagnosed.
Project description:ObjectiveTo determine the recurrence risk of ictal asystole (IA) and its determining factors in people with epilepsy.MethodsWe performed a systematic review of published cases with IA in 3 databases and additionally searched our local database for patients with multiple seizures simultaneously recorded with ECG and EEG and at least one IA. IA recurrence risk was estimated by including all seizures without knowledge of the chronological order. Various clinical features were assessed by an individual patient data meta-analysis. A random mixed effect logistic regression model was applied to estimate the average recurrence risk of IA. Plausibility of the calculated IA recurrence risk was checked by analyzing the local dataset with available information in chronological order.ResultsEighty patients with 182 IA in 537 seizures were included. Recurrence risk of IA amounted to 40% (95% confidence interval [CI] 32%-50%). None of the clinical factors (age, sex, type and duration of epilepsy, hemispheric lateralization, duration of IA per patient) appeared to have a significant effect on the short-term recurrence risk of IA. When considering the local dataset only, IA recurrence risk was estimated to 30% (95% CI 14%-53%). Information whether IA coincided with symptoms (i.e., syncope) or not was given in 60 patients: 100 out of 142 IAs were symptomatic.ConclusionOur data suggest that in case of clinically suspected IA, the recording of 1 or 2 seizures is not sufficient to rule out IA. Furthermore, the high short-term recurrence risk favors aggressive treatment, including pacemaker implantation if seizure freedom cannot be achieved.
Project description:BackgroundThird-degree atrioventricular (AV) block can result in sudden cardiac death if no reliable escape rhythm is present. Here, we report a case of an 86-year-old female patient who developed a third-degree AV block leading to cardiac arrest. Surprisingly, sinus rhythm returned after 4?min of asystole, and she showed complete neurological recovery.Case summaryEmergency services were contacted by the husband of an 86-year-old woman after she was found unconscious. Ambulance personnel diagnosed a third-degree AV block without an escape rhythm and transcutaneous pacing was started. At arrival on the emergency ward, pacing was inadequate, resulting in absence of circulation for ?10 min. After consultation with the family, the patient turned out to have signed a 'do not resuscitate' order. Given the impression that the considerable delay deemed favourable neurological recovery unlikely, it was decided together with the family to stop the resuscitation. Subsequently, she had an intermittent junctional escape rhythm but eventually developed a documented asystole of more than 4?min. Against all expectations, she regained sinus rhythm and fully recovered. Eventually, a pacemaker was implanted and she was discharged home without neurological sequalae of the cardiac arrest.DiscussionAutoresuscitation, also known as the Lazarus syndrome, is the spontaneous return of circulation after cardiac arrest and is incidentally seen after failed cardiopulmonary resuscitation (CPR). Autoresuscitation in the absence of CPR is highly unusual, but could, in this case, be due to the total AV block as the cause of the cardiac arrest.
Project description:BackgroundThe Bezold-Jarisch reflex (BJR) is a cardioinhibitory parasympathetic response to activation of ventricular mechanoreceptors, which can result in bradycardia, atrioventricular block, or asystole. This phenomenon has been triggered by acute myocardial ischaemia, intra-arterial nitroglycerine use, natriuretic peptides, and with exceptional rarity, in middle-aged women only, by dobutamine infusion during stress echocardiography.Case summaryWe present the case of a 61-year-old woman who suffered a 5.1-s sinus pause during her 20 μg/kg/min infusion of dobutamine. Recovery was immediate following termination of dobutamine infusion. Concurrent echocardiography was normal, and subsequent cardiac catheterization and electrophysiologic study were normal.DiscussionThis is the fifth documented case of a severe BJR causing asystole during dobutamine infusion, which adds to the accumulating evidence supporting the benign nature of the condition.
Project description:Recent studies have interpreted patterns of remotely sensed tree cover as evidence that forest with intermediate tree cover might be unstable in the tropics, as it will tip into either a closed forest or a more open savanna state. Here we show that across all continents the frequency of wildfires rises sharply as tree cover falls below ~40%. Using a simple empirical model, we hypothesize that the steepness of this pattern causes intermediate tree cover (30?60%) to be unstable for a broad range of assumptions on tree growth and fire-driven mortality. We show that across all continents, observed frequency distributions of tropical tree cover are consistent with this hypothesis. We argue that percolation of fire through an open landscape may explain the remarkably universal rise of fire frequency around a critical tree cover, but we show that simple percolation models cannot predict the actual threshold quantitatively. The fire-driven instability of intermediate states implies that tree cover will not change smoothly with climate or other stressors and shifts between closed forest and a state of low tree cover will likely tend to be relatively sharp and difficult to reverse.
Project description:We study second-order partial differential equations (PDEs) in four dimensions for which the conformal structure defined by the characteristic variety of the equation is half-flat (self-dual or anti-self-dual) on every solution. We prove that this requirement implies the Monge-Ampère property. Since half-flatness of the conformal structure is equivalent to the existence of a non-trivial dispersionless Lax pair, our result explains the observation that all known scalar second-order integrable dispersionless PDEs in dimensions four and higher are of Monge-Ampère type. Some partial classification results of Monge-Ampère equations in four dimensions with half-flat conformal structure are also obtained.
Project description:Introduction:The integrase strand transfer inhibitor dolutegravir (DTG) has a high genetic barrier to resistance. Only rare cases of resistance to DTG have been reported when it is used as a component of antiretroviral therapy regimens in treatment-experienced patients unless there was prior use of a first-generation integrase inhibitor. Patient presentation:A 38-year-old woman diagnosed with tuberculosis was switched to a second-line antiretroviral regimen of zidovudine, lamivudine and dolutegravir 50 mg 12-hourly together with rifampicin-based TB treatment. Based on treatment history and a previous resistance test there was resistance to lamivudine but full susceptibility to zidovudine. The patient did not suppress her viral load on this regimen and later admitted to only taking dolutegravir 50 mg in the morning because of insomnia. Management and outcome:A second resistance test was performed which showed intermediate level of resistance to dolutegravir. Her regimen was changed to tenofovir, emtricitabine and ritonavir-boosted atazanavir with rifabutin replacing rifampicin for the remainder of her TB treatment. She achieved viral suppression on this regimen. Conclusion:To our knowledge this is the first case report from South Africa of emergent dolutegravir resistance in a treatment-experienced, integrase inhibitor-naïve patient. Factors that may have contributed to resistance emergence in this patient were that there was only one fully active nucleoside reverse transcriptase inhibitor in the regimen and lower exposure to dolutegravir because of the reduced dosing frequency while on rifampicin.
Project description:Metastatic pheochromocytoma and paraganglioma (mPHEO/PGL) are frequently associated with succinate dehydrogenase B (SDHB) mutations. Cyclophosphamide-dacarbazine-vincristine (CVD) regimen is recommended as standard chemotherapy for advanced mPHEO/PGL. There is limited evidence to support the role of metronomic schemes (MS) of chemotherapy in mPHEO/PGL treatment. We report 2 patients with SDHB-related mPGL who received a regimen consisting of MS temozolomide (TMZ) and high-dose lanreotide after progression on both CVD chemotherapy and high-dose lanreotide. Molecular profiling of the tumor tissue from both patients revealed hypermethylation of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter. In one patient, progression-free survival was 13?months and the second patient remained under treatment after 27?months of stabilization of metabolic response of his disease. Treatment was well tolerated, and adverse effects were virtually absent. A modification in the scheme of TMZ from standard schemes to MS is safe and feasible and can be considered in patients with progressive mPHEO/PGL refractory to dacarbazine in standard doses.
Project description:Cervical cancer is the fourth most common malignant disease among women, with metastatic disease having a dismal survival rate compared to localized disease when using standard combination chemotherapy. Next-generation sequencing (NGS) of tumors has allowed for targeted treatments of cancers in patients who have progressed on first-line therapy. We present a case of a 46 year-old female with advanced cervical adenocarcinoma and metastatic recurrence in the lungs found to have HER2 mutation who underwent first and second-line HER2-targeted therapy with sustained disease response. We review the standard of care for advanced cervical cancer, toxicity profiles of chemotherapy and immunotherapy that were employed, the economics of NGS and targeted treatment, and future directions for HER2-targeted therapy. This case report highlights a patient with metastatic cervical cancer responsive to first and second-line HER2-targeted therapy.