Coping as a resource to allow for psychosocial adjustment in fatal disease: results from patients with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing. Methods: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded. Results: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS. Conclusion: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.

Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

BACKGROUND: Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)

Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value.

Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case-control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.

Seasonal patterns and associations in the incidence of acute ischemic stroke requiring mechanical thrombectomy.

BACKGROUND: In order to identify risk periods with an increased demand in technical and human resources, we tried to determine patterns and associations in the incidence of acute ischemic stroke due to embolic large vessel occlusions (eLVO) requiring mechanical thrombectomy (MT). METHODS: We conducted a time series analysis over a 9-year period (2010-2018) based on observational data in order to detect seasonal patterns in the incidence of MT due to eLVO (n = 2628 patients). In a series of sequential negative binominal regression models, we aimed to detect further associations (e.g., temperature, atmospheric pressure, air pollution). RESULTS: There was a 6-month seasonal pattern in the incidence of MT due to eLVO (p = 0.024) peaking in March and September. Colder overall temperature was associated with an increase in MT due to eLVO (average marginal effect [AME], [95% CI]: -0.15 [-0.30-0.0001]; p = 0.05; per °C). A current increase in the average monthly temperature was associated with a higher incidence of MT due to eLVO (0.34 [0.11-0.56]; p = 0.003). Atmospheric pressure was positively correlated with MT due to eLVO (0.38 [0.13-0.64]; p = 0.003; per hectopascal [hPa]). We could detect no causal correlation between air pollutants and MT due to eLVO. CONCLUSIONS: Our data suggest a 6-month seasonal pattern in the incidence of MT due to eLVO peaking in spring and early autumn. This might be attributed to two different factors: (1) a current temperature rise (comparing the average monthly temperature in consecutive months) and (2) colder overall temperature. These results could help to identify risk periods requiring an adaptation in local infrastructure.

Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): Rationale and study design.

Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.

Gain and loss of extracellular molecules in sporadic inclusion body myositis and polymyositis--a proteomics-based study.

Sporadic inclusion body myositis (sIBM) contains non-necrotic myofibers that are surrounded and/or invaded by inflammatory cells. In this study we aimed to identify selective molecules that are present at this site. Myofibers of four biopsies of sIBM that were surrounded and/or invaded by inflammatory cells were microdissected, pooled and profiled by proteomic studies using mass spectrometry. Normal skeletal muscle tissue served as control. Based on the table of proteins that were detected in sIBM only, we selected nine extracellular matrix molecules and validated the results performing immunofluorescence. Seven out of nine proteins that were detected in sIBM by mass spectrometry showed different immunohistochemical results in myositis and normal controls. Of these, the small leucine-rich repeat proteins proline arginine-rich end leucine-rich repeat protein (PRELP) and biglycan were deposited precisely at myofibers surrounded and/or invaded by inflammatory cells both in sIBM and polymyositis. The basement membrane (BM) molecules merosin, perlecan, nidogen-2 and collagen IV were variably destroyed or increased at these sites. P component, which ensheathed all myofibers in normal controls, was absent from invaded myofibers. Similar to BM remodeling, the specific deposition of PRELP and biglycan may represent a mechanism to defend against immune attack. Loss of P component may affect the anchorage of the myofiber in the endomysium.

The modified Bose method for the endovascular treatment of intracranial atherosclerotic arterial stenoses using the Enterprise stent.

BACKGROUND: Balloon dilatation and deployment of a self-expanding stent is a safe treatment for intracranial atherosclerotic stenoses. The significant recurrence rate might be related to the high radial force of the Wingspan stent. OBJECTIVE: To evaluate the procedural safety and stenosis recurrence rate by the use of a stent with reduced radial force (Enterprise). METHODS: Two hundred nine atherosclerotic stenoses (189 patients) were treated (median age, 68 years; 132 male) in a single center. Lesion locations included internal carotid artery (n = 27), middle cerebral artery (n = 62), vertebral artery (n = 64), basilar artery (n = 55), and posterior cerebral artery (n = 1). Pre- and postmedication included acetylsalicylic acid and Clopidogrel for at least 12 months. Preprocedural and follow-up examinations included magnetic resonance imaging (MRI), neurological assessment, and digital subtraction angiography (6, 12, 26, and 52 weeks). Data registry included age, sex, normal vessel diameter, degree of stenosis, residual stenosis after stent, minimal in-stent diameter, and occurrence of ischemic symptoms during follow-up. RESULTS: Median pre- and postprocedural stenosis rate was 65.4 ± 1% vs 25.1 ± 1%. Technical success rate was 100%. Major procedural complications occurred in 16 patients (8.1%). Combined neurological morbidity and mortality rate at 30 days was 2 patients (0.9%). In 174 stenoses (83%) angiographic follow-up was obtained (mean, 10.2 months). A restenosis (>50%) was observed in 43 (24.7%) cases after 4.2 months (mean) with 4 (9.3%) symptomatic lesions. Incidence of recurrent ischemia related to the stented artery was 2.2% during 10.2 months of mean follow-up. CONCLUSION: Undersized balloon angioplasty and deployment of an Enterprise stent is safe and effective for intracranial stenoses. Follow-up results were equal to or better than those reported for bare-metal balloon-expandable or self-expanding stents and yielded excellent protection from recurrent ischemia.

Cardiovascular magnetic resonance imaging (CMR) reveals characteristic pattern of myocardial damage in patients with mitochondrial myopathy.

BACKGROUND: Mitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfunction of the mitochondrial respiratory chain. No comprehensive and targeted cardiovascular magnetic resonance (CMR) studies have been performed so far in patients with mitochondrial disorders. The present study aimed at characterising cardiac disease manifestations in patients with mitochondrial myopathy and elucidating the in vivo cardiac damage pattern of patients with different subforms of mitochondrial disease by CMR studies. METHODS AND RESULTS: In a prospective study, 37 patients with mitochondrial myopathy underwent comprehensive neurological and cardiac evaluations including physical examination, resting ECG and CMR. The CMR studies comprised cine-CMR, T2-weighted "edema" imaging and T1-weighted late-gadolinium-enhancement (LGE) imaging. Various patterns and degrees of skeletal myopathy were present in the participants of this study, whereas clinical symptoms such as chest pain symptoms (in eight (22%) patients) and various degrees of dyspnea (in 16 (43%) patients) were less frequent. Pathological ECG findings were documented in eight (22%) patients. T2-weighted "edema" imaging was positive in one (3%) patient with MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) only. LGE imaging demonstrated the presence of non-ischemic LGE in 12 (32%) patients: 10 out of 24 (42%) patients with CPEO (chronic progressive external ophthalmoplegia) or KSS (Kearns-Sayre syndrome) and 2 of 3 (67%) patients with MELAS were LGE positive. All 10 LGE-positive patients with CPEO or KSS demonstrated a potentially typical pattern of diffuse intramural LGE in the left-ventricular (LV) inferolateral segments. CONCLUSIONS: Cardiac involvement is a frequent finding in patients with mitochondrial myopathy. A potentially characteristic pattern of diffuse intramural LGE in the LV inferolateral segments was identified in patients suffering from the subforms CPEO or KSS.

Novel missense mutation p.A310P in the GNE gene in autosomal-recessive hereditary inclusion-body myopathy/distal myopathy with rimmed vacuoles in an Italian family.

Autosomal-recessive hereditary inclusion-body myopathy with relative quadriceps sparing is associated with mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Two Italian sisters affected with autosomal-recessive hIBM were shown to be compound heterozygous for a novel GNE mutation: a p.A310P amino acid change along with a p.R246W mutation on the second allele both in the epimerase domain. This is the first mutation event observed in a human GNE allele inducing a proline. Muscle biopsy showed abundant rimmed and non-rimmed vacuoles. Severe disease progression was noted in the elder sister. The Italian family further expands the wide phenotypic and genotypic spectrum of hIBM.

Isolated bilateral blindness as the sole manifestation of transient ischaemic attacks.

PURPOSE: To explain the rare phenomenon of acute transient bilateral blindness without additional ophthalmological or neurological symptoms and signs. METHODS: Six patients with isolated bilateral visual loss lasting 1-15 mins and occurring simultaneously in both eyes were evaluated. Clinical observation, neuroimaging (CT, MRI, MR-angiography), extra- and transcranial Doppler and vascular risk factors assessment were performed. RESULTS: Cortical blindness due to bilateral occipital lobe transient ischaemic attacks (TIAs) was established as the most likely cause of acute transient visual loss in all patients. CONCLUSION: We suggest that in cases of transient bilateral blindness with sudden onset, appearing simultaneously in both visual fields, a bilateral ischaemia of the visual cortex should be suspected even if other neurological symptoms are lacking. Patients should be managed in the same way as patients with vertebrobasilar TIAs.