Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness

Congenital myasthenic syndrome (CMS) is a heterogeneous disorder that causes fatigable muscle weakness. CMS has been associated with variants in the MuSK gene and, to date, 16 patients have been reported. MuSK‐CMS patients present a different phenotypic pattern of limb girdle weakness. Here, we describe four additional patients and discuss the phenotypic and clinical relationship with those previously reported. Two novel damaging missense variants are described: c.1742T > A; p.I581N found in homozygosis, and c.1634T > C; p.L545P found in compound heterozygosis with p.R166*. The reported patients had predominant limb girdle weakness with symptom onset at 12, 17, 18, and 30 years of age, and the majority exhibited a good clinical response to Salbutamol therapy, but not to esterase inhibitors. Meta‐analysis including previously reported variants revealed an increased likelihood of a severe, respiratory phenotype with null alleles. Missense variants exclusively affecting the kinase domain, but not the catalytic site, are associated with late onset. These data refine the phenotype associated with MuSK‐related CMS.     

Teaching of leprosy: current challenges

In the context of declining leprosy endemicity worldwide, keeping the interest in knowledge and expertise in leprosy alive has been a matter of concern. Approaching the problem only in primary care, without the proper integration with other levels of care in the health system fails to account for the complexity of the disease. Training professionals to work at different levels of health care is a current challenge. The objective of this review was to look for experiences related to the teaching of leprosy both in undergraduate courses in the field of health sciences and in training programs for professionals who work in patient care. We highlight the role of the dermatologist in the management of control programs, diagnosis and treatment of the disease, as well as in the continuous education of other health professionals.     

Myocardial perfusion MRI shows impaired perfusion of the mouse hypertrophic left ventricle

There is growing consensus that myocardial perfusion deficits play a pivotal role in the transition from compensated to overt decompensated hypertrophy. The purpose of this study was to systematically study myocardial perfusion deficits in the highly relevant model of pressure overload induced hypertrophy and heart failure by transverse aortic constriction (TAC), which was not done thus far. Regional left ventricular (LV) myocardial perfusion (mL/min/g) was assessed in healthy mice (n = 6) and mice with TAC (n = 14). A dual-bolus first-pass perfusion MRI technique was employed to longitudinally quantify myocardial perfusion values between 1 and 10 weeks after surgery. LV function and morphology were quantified from cinematographic MRI. Myocardial rest perfusion values in both groups did not change significantly over time, in line with the essentially constant global LV function and mass. Myocardial perfusion was significantly decreased in TAC mice (4.2 ± 0.9 mL/min/g) in comparison to controls (7.6 ± 1.8 mL/min/g) (P = 0.001). No regional differences in perfusion were observed within the LV wall. Importantly, increased LV volumes and mass, and decreased ejection fraction correlated with decreased myocardial perfusion (P < 0.001, in all cases). Total LV blood flow was decreased in TAC mice (0.5 ± 0.1 mL/min, P < 0.001) in comparison to control mice (0.7 ± 0.2 mL/min). Myocardial perfusion in TAC mice was significantly reduced as compared to healthy controls. Perfusion was proportional to LV volume and mass, and related to decreased LV ejection fraction. Furthermore, this study demonstrates the potential of quantitative first-pass contrast-enhanced MRI for the study of perfusion deficits in the diseased mouse heart.     

Study of the Determinants of Vitamin D Status in Pediatric Patients With Osteogenesis Imperfecta

Objective: Vitamin D is essential to the development and maintenance of the skeleton, especially for children with bone disorders such as osteogenesis imperfecta (OI). We evaluated serum 25-hydroxyvitamin D (25-OHD) levels to assess the relationship between determinants of vitamin D status in pediatric patients with OI.

Methods: This cross-sectional study evaluated sex, age, weight, height, body mass index, OI type, sunscreen use, season of assessment, sun exposure, vitamin D and calcium supplementation, bisphosphonate treatment, bone mineral density (BMD), milk and soda consumption, mobility, and time of sedentary activity. Levels of serum 25-OHD, calcium, parathyroid hormone (PTH), phosphorus, and alkaline phosphatase (ALP) were analyzed. Serum levels of 25-OHD were classified according to sufficient (>30 ng/ml or 75 nmol/L), insufficient (20–30 ng/ml or 50–75 nmol/L), moderately deficient (20–10 ng/ml or 50–25 nmol/L), and severely deficient (<10 ng/ml or 25 nmol/L).

Results: Fifty-two patients were included and 46 (88.4%) were classified as having insufficient or deficient 25-OHD. An inverse correlation between serum 25-OHD and time of sedentary activity (r = ?0.597, p < 0.001) and a positive correlation with height (r = 0.521, p = 0.046) and whole body BMD (r = 0.586, p = 0.022) were observed. A significant difference between the number of glasses of milk consumed (p = 0.010) was observed.

Conclusion: To optimize bone health, patients with OI need to be educated regarding habits that can improve serum 25-OHD levels, such as a reduction in periods of inactivity, the importance of sun exposure, and increasing consumption of milk and fortified dairy products.     

Epilepsy and stigma: an approach to understanding through the life and works of the Brazilian writer Machado de Assis (1839-1908)

Machado de Assis (1839-1908)-novelist, short story writer, essayist, and poet-is a fascinating personality. Had he written in French, English, German, or Italian, he would have achieved universal fame and would be in the same company as Balzac, Tolstoy, Dickens, and Dostoevsky. This article discusses stigma in epilepsy through Machado de Assis' life, literary work, and letters to other Brazilian writers. Founder of the Brazilian Academy of Letters, Machado offers an insoluble enigma to psychologists and essayists. Born in stark poverty, feeble, and ugly, he had to fight the taint of epilepsy. The documentation of epilepsy in Machado de Assis' texts and letters and the testimony of his contemporaries is unique, allowing the comprehension of scientific concepts and stigma related to epilepsy in the 19th century, when the positivist ideas of the Italian neuropsychiatrist Cesare Lombroso (1835-1909) permeated nascent Brazilian neuropsychiatry. Much of the stigma associated with epilepsy we witness today emerged from these concepts. Even today in Brazil, when barbaric crimes are committed, headlines in newspapers produced by forensic psychiatrists often attribute the conduct of the criminal to epileptic behavior.     

Nutritional risk factors for postoperative complications in Brazilian elderly patients undergoing major elective surgery

OBJECTIVE: In this prospective study, we assessed nutritional and immunologic risk factors for infectious complications and deaths related to infection in elderly patients undergoing major elective surgery. METHODS: Seventy patients 60 y or older were enrolled in this study. The preoperative variables analyzed were body mass index, body mass index knee height, triceps skinfold, subscapular skinfold, mid-arm muscle circumference, mid-arm muscle area, albumin, transferrin, prealbumin, and retinol-binding protein levels, immunoglobulins G, A, and M, C3, and C4 levels, total lymphocyte counts, and the occurrence of delayed hypersensitivity reactions (multitest). RESULTS: Abnormally low levels of prealbumin (P = 0.004), retinol-binding protein (P = 0.05), and transferrin (P = 0.04) were related to infectious complications. Prealbumin levels (P = 0.02) and lymphocyte counts below 1500 cells/mm(3) (P = 0.04) were associated with mortality secondary to infection. Univariate regression analysis showed that levels of prealbumin (P = 0.02, odds ratio = 13.3, 95% confidence limits = 1.6, 110.9), retinol-binding protein (P = 0.03, odds ratio = 4.8, 95% confidence limits = 1.2, 19.3), and transferrin (P = 0.03; odds ratio = 4.2, 95% confidence limit = 1.2, 15.6) were associated with infectious complications. Multivariate analysis associated only prealbumin levels with infectious complications (P = 0.02, odds ratio = 13.3, 95% confidence limit = 1.6, 110.9). Regression analysis provided no conclusion regarding mortality because of the small number of deaths recorded. CONCLUSIONS: In patients with a good cardiac index (Goldman I and II) who underwent major elective surgery, prealbumin protein, retinol-binding protein, and transferrin levels below normal values represented a significant risk for postoperative infectious complications. Lymphocyte counts lower than 1500/m(3) and abnormal prealbumin values were associated with postoperative mortality secondary to infection. The anthropometric variables evaluated did not predict postoperative infectious complications and mortality.     

Modulation of epileptiform EEG discharges in juvenile myoclonic epilepsy: an investigation of reflex epileptic traits

Purpose: Previous studies have suggested that cognitive tasks modulate (provoke or inhibit) the epileptiform electroencephalography (EEG) discharges (EDs) in patients with juvenile myoclonic epilepsy (JME). Their inhibitory effect was found to be especially frequent (64–90%). These studies arbitrarily defined modulation as a >100% increase or >50% decrease of the EDs compared with baseline, which may not sufficiently distinguish from spontaneous fluctuations. The aim of our study was to assess the modulation of EDs and the precipitation of myoclonic seizures by cognitive tasks and by conventional provocation methods, taking into account also the spontaneous fluctuation of EDs. Method: Sixty patients with JME underwent video‐EEG recordings including 50‐min baseline, sleep, hyperventilation, intermittent photic stimulation (IPS), and cognitive tasks. To account for spontaneous fluctuations of the EDs we divided the baseline period into 5‐min epochs and calculated the 95% confidence interval for the baseline EDs in each patient. Modulation was assumed when the number of EDs during any 5‐min test period was outside the 95% confidence interval. Key Findings: Using the arbitrary method, our results were similar to previous publications: Cognitive tasks seemed to inhibit the EDs in 94% of the patients, and to provoke them in 22%. However, when the spontaneous fluctuations were accounted for, inhibition was found in only 29% of the patients and provocation in 18%. A nonspecific effect of any cognitive task seemed to account for the observed significant inhibition in two‐thirds of the cases, but was observed in only one of the patients with significant provocation. Photoparoxysmal response was observed in 23% of the patients. When accounting for the spontaneous occurrence of EDs, IPS had provocative effect in 10% of the patients. Hyperventilation and sleep had provocative effect on EDs to an extent similar to the cognitive tasks (hyperventilation: 22%; sleep: 18%). The conventional provocation methods tended to be more efficient in patients who were not seizure free. Myoclonia were recorded most often during the cognitive tasks (10 patients). Significance: Spontaneous fluctuations of EDs account for most of the previously described inhibitory effect of the cognitive tasks. The provocative effect of the cognitive tasks is task‐specific, whereas the inhibitory effect seems to be related to cognitive activation in general.