Published data on treatment of fatty acid oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain fatty acid oxidation ...defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain fatty acid oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are associated with the most severe clinical picture and require a strict fat-reduced and fat-modified (medium-chain triglyceride-supplemented) diet. Many patients still suffer acute life-threatening events or long-term neuropathic symptoms despite adequate treatment, and newborn screening has not significantly changed the prognosis for these severe phenotypes. Very long-chain acyl-CoA dehydrogenase deficiency recognized in neonatal screening, in contrast, frequently has a less severe disease course and dietary restrictions in many patients may be loosened. On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain fatty acid oxidation defects.
Chordoma is a rare malignant tumor of bone with high morbidity and mortality. Recently, aggressive pediatric poorly differentiated chordoma with SMARCB1 loss has been described. This study summarizes ...the clinicopathologic features of poorly differentiated chordoma with SMARCB1 loss in the largest series to date. A search of records between 1990-2017 at MGH identified 19 patients with poorly differentiated chordoma. Immunohistochemical stains were evaluated. Kaplan-Meier survival statistics and log-rank (Mantel Cox) tests compared survival with other subtypes. The patients (n = 19) were diagnosed at a median age of 11 years (range: 1-29). Tumors arose in the skull base and clivus (n = 10/19; 53%); cervical spine (n = 6/19; 32%); and sacrum or coccyx (n = 3/19; 16%). The clinical stage of these patients (AJCC 7e) was stage 2A (n = 7/16; 44%); stage 2B (n = 6/16; 38%); stage 4A (n = 1/16; 6%); and stage 4B (n = 2/16; 13%). The tumors were composed of sheets of epithelioid cells with nuclear pleomorphism, abundant eosinophilic cytoplasm, and increased mitoses. Tumors were positive for cytokeratin (n = 18/18; 100%) and brachyury (n = 18/18; 100%). Patients were treated with a combination of excision, radiation therapy, and chemotherapy. No difference in overall survival, progression free survival, local control time, and metastasis free survival was identified between poorly differentiated chordoma of the skull base and of the spine. Compared to other chordoma subtypes, poorly differentiated chordoma has a significantly decreased mean overall survival after stratification by site (p = 0.037). Pediatric poorly differentiated chordoma has a distinct clinical and immunohistochemical profile, with characteristic SMARCB1 loss and decreased survival compared to conventional/chondroid chordoma. Recognition of this subtype is important because these malignancies should be treated aggressively with multimodality therapy.
Objective:
To determine the presence and kinetics of antibodies against synaptic proteins in patients with herpes simplex virus encephalitis (HSE).
Methods:
Retrospective analysis of 44 patients with ...polymerase chain reaction‐proven HSE for the presence of a large panel of onconeuronal and synaptic receptor antibodies. The effect of patients' serum was studied in cultures of primary mouse hippocampal neurons.
Results:
N‐Methyl‐D‐aspartate receptor (NMDAR) antibodies of the immunoglobulin (Ig) subtypes IgA, IgG, or IgM were detected in 13 of 44 patients (30%) in the course of HSE, suggesting secondary autoimmune mechanisms. NMDAR antibodies were often present at hospital admission, but in some patients developed after the first week of HSE. Antibody‐positive sera resulted in downregulation of synaptic marker proteins in hippocampal neurons.
Interpretation:
Some patients with HSE develop IgA, IgG, or IgM autoantibodies against NMDAR. Sera from these patients alter the density of neuronal synaptic markers, suggesting a potential pathogenic disease‐modifying effect. These findings have implications for the understanding of autoimmunity in infectious diseases, and prospective studies should reveal whether the subgroup of patients with HSE and NMDAR antibodies may benefit from immunotherapy. ANN NEUROL 2012;72:902–911
Pelvic congestion syndrome is defined as chronic pelvic pain due to incompetent (dilated and refluxing) pelvic veins. The aim of this study was to investigate the prevalence of this condition by ...examining the prevalence of dilated ovarian and para-uterine veins in pre- and postmenopausal female patients, irrespective of their symptoms. We subsequently investigated how many women with dilated veins suffered from chronic pelvic pain. Additionally, we attempted to define diagnostic criteria that may allow for early identification of affected patients.
We reassessed 2384 abdomino-pelvic computed tomography scans performed on women at our institution. The maximal diameters of the ovarian and para-uterine veins were measured. Patients with a pathological process in the abdomen or pelvis affecting the veins were excluded. We considered ovarian vein dilation to be 6 mm or more in the axial plane. For patients that met these criteria, we performed a retrospective chart review to evaluate the clinical presentation and/or symptoms of these patients.
Dilated pelvic veins were present in 293/2384 (12%) patients, 118/559 premenopausal (21%) and 175/1825 postmenopausal (10%). Chronic pelvic pain of unclear etiology had been documented prior to the CT in 54/293 (18%) women with dilated veins-2% of the whole study collective (54/2384); 8% of all premenopausal (44/559) and 0.5% of all postmenopausal (10/1825). It was often accompanied by urological symptoms such as hematuria, dysuria, and urinary frequency, in the absence of infection (p<0.05). We identified a strong correlation between the presence of dilated ovarian veins and chronic pelvic pain in premenopausal parous patients with hematuria.
Pelvic congestion syndrome appears to be an underdiagnosed and undertreated disease. In our study, 8% of all premenopausal women had documented chronic pelvic pain of unclear etiology and dilated ovarian and pelvic veins on cross-sectional imaging studies. The features we identified in this study as most relevant should enable a faster identification of patients who could benefit from a specific treatment regimen for this condition.
We show that the evidence for a local arrow of time, which is equivalent to the entropy production in thermodynamic systems, can be decomposed. In a system with many degrees of freedom, there is a ...term that arises from the irreversible dynamics of the individual variables, and then a series of non-negative terms contributed by correlations among pairs, triplets, and higher-order combinations of variables. We illustrate this decomposition on simple models of noisy logical computations, and then apply it to the analysis of patterns of neural activity in the retina as it responds to complex dynamic visual scenes. We find that neural activity breaks detailed balance even when the visual inputs do not, and that this irreversibility arises primarily from interactions between pairs of neurons.
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