Focal Peripheral Neuropathies, 4th ed.

This is a review of a new edition of JD Stewart's <em>Focal Peripheral Neuropathies</em

Role of Methionine in Fetal Development of Beef Cattle

The objective of this study was to evaluate whether total amino acids (AA) or methionine have an effect on fetal programming of calves using 108 Angus Brangus cows. Treatments were 1) Control, limpograss hay with molasses plus urea (16% CP as fed basis) at 2.72 kg./hd/d, 2) Fishmeal, Control plus 0.33 kg./hd/d of fishmeal ( methionine 2.85 % of RUP), and 3) Methionine, Control plus 10 g/hd/d of MetaSmart liquid (Addisseo Alpharetta, GA) . Fishmeal and Methionine treatments supplied similar amounts of metabolizable methionine. Weight of cows and calves along with body condition score of cows were measured at the start and end of the 120 day supplementation period, and milk yield was measured at 3 time points by weigh-suckle-weigh technique. In Year 2, 24 steer calves conceived during the treatment period in Year 1 were fed individually during a metabolism experiment following weaning at approximately 7 months of age. Body weight, feed intake, plasma metabolites, and nutrient digestibility were measured in steers during the metabolism experiment. Body weight and body condition score change of cows were not different among treatments during the treatment period in Year 1. Treatment did not affect calf weight gain even though there was a trend for Methionine dams to have greater energy-corrected milk yield and for Fishmeal and Methionine dams to have greater milk protein content than Control dams. In Year 2, treatment did not affect weaning weight of calves conceived during the treatment period in Year 1. During the post weaning metabolism experiment, Average daily gain, final body weight (FBW), and gain: feed ratio were greater in steers whose dams supplemented with Fishmeal or Methionine during early gestation. Steers born to Control and Methionine dams had greater plasma urea nitrogen concentrations before and after feeding, and tended to have greater change in plasma urea nitrogen concentration than steers born to Fishmeal dams. Steers born to Methionine dams had lower plasma glucose concentration before and after feeding, but greater change in plasma glucose concentration than steers born to Fishmeal dams. There was a trend for treatment to effect Neutral detergent fiber (NDF) and Acid detergent fiber (ADF) digestibility with steers born to Methionine dams having greater digestibility than steers born to Control or Fishmeal dams. In conclusion, methionine is a key nutrient in fetal programming and can be used in conjunction with poor quality forage to improve performance of offspring

Access to Immunoglobulin Treatment for CIDP Patients During the COVID-19 Pandemic

Background: Immunoglobulin supplies are limited; their access for patients diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may have been difficult during the COVID-19 pandemic. Methods: A retrospective cross-sectional study was conducted with CIDP patients (n=16, 68.8% female, mean age 60.4±11.3) recruited from three Montreal tertiary care institutions. Inclusion criteria were patients over 18 years old who were receiving immunoglobulin treatment as of March 1st, 2020. Patients were asked to complete a questionnaire inquiring about changes in their immunoglobulin treatment during the pandemic and about their quality of life. Their charts were reviewed by an independent investigator. We used weighted chi-squared statistical tests and Cramer’s V correlation ratios to measure associations with treatment change. Results: Eighteen months after the pandemic started, 50% of patients were receiving the same treatment, 25% were receiving immunoglobulin treatment at a different frequency, 6.3% were receiving a different dose, 12.5% were receiving a different dose and frequency, and 6.3% were receiving a different treatment. Reasons associated with treatment change were worsening of neurological condition (18.8%; Cramer’s V=0.480; p-value=0.055), improvement of neurological condition (25%; Cramer’s V=0.577; p-value=0.021) and reduced availability of treatment (6.3%; Cramer’s V=0.258; p-value=0.302). There were no significant correlations between lower quality of life (p-value=0.323) or lower Rasch-built Overall Disability Scale score (p-value=0.574) and treatment change.  Conclusion: Difficulty accessing immunoglobulin treatment was infrequent and not significantly associated with treatment change for CIDP patients during the COVID-19 pandemic. A larger multicentre study across multiple sites might identify other treatment access problems resulting from the pandemic

Glibenclamide reverses cardiovascular abnormalities of Cantu syndrome driven by KATP channel overactivity

Cantu syndrome (CS) is a complex disorder caused by gain-of-function (GoF) mutations in ABCC9 and KCNJ8, which encode the SUR2 and Kir6.1 subunits, respectively, of vascular smooth muscle (VSM) KATP channels. CS includes dilated vasculature, marked cardiac hypertrophy, and other cardiovascular abnormalities. There is currently no targeted therapy, and it is unknown whether cardiovascular features can be reversed once manifest. Using combined transgenic and pharmacological approaches in a knockin mouse model of CS, we have shown that reversal of vascular and cardiac phenotypes can be achieved by genetic downregulation of KATP channel activity specifically in VSM, and by chronic administration of the clinically used KATP channel inhibitor, glibenclamide. These findings demonstrate that VSM KATP channel GoF underlies CS cardiac enlargement and that CS-associated abnormalities are reversible, and provide evidence of in vivo efficacy of glibenclamide as a therapeutic agent in CS

Clinical, paraclinical and serological findings in Susac syndrome: an international multicenter study

Background: Susac syndrome (SuS) is a rare disorder thought to be caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear leading to central nervous system (CNS) dysfunction, visual disturbances due to branch retinal artery occlusions (BRAO), and hearing deficits. Recently, a role for anti-endothelial cell antibodies (AECA) in SuS has been proposed. Objectives: To report the clinical and paraclinical findings in the largest single series of patients so far and to investigate the frequency, titers, and clinical relevance of AECA in SuS. Patients and methods: A total of 107 serum samples from 20 patients with definite SuS, 5 with abortive forms of SuS (all with BRAO), and 70 controls were tested for AECA by immunohistochemistry employing primate brain tissue sections. Results: IgG-AECA >1:100 were detected in 25% (5/20) of patients with definite SuS and in 4.3% (3/70) of the controls. Median titers were significantly higher in SuS (1:3200, range 1:100 to 1:17500) than in controls (1:100, range 1:10 to 1:320); IgG-AECA titers >1:320 were exclusively present in patients with SuS; three controls had very low titers (1:10). Follow-up samples (n = 4) from a seropositive SuS patient obtained over a period of 29 months remained positive at high titers. In all seropositive cases, AECA belonged to the complement-activating IgG1 subclass. All but one of the IgG-AECA-positive samples were positive also for IgA-AECA and 45% for IgM-AECA. SuS took a severe and relapsing course in most patients and was associated with bilateral visual and hearing impairment, a broad panel of neurological and neuropsychological symptoms, and brain atrophy in the majority of cases. Seropositive and seronegative patients did not differ with regard to any of the clinical or paraclinical parameters analyzed. Conclusions: SuS took a severe and protracted course in the present cohort, resulting in significant impairment. Our finding of high-titer IgG1 and IgM AECA in some patients suggest that humoral autoimmunity targeting the microvasculature may play a role in the pathogenesis of SuS, at least in a subset of patients. Further studies are warranted to define the exact target structures of AECA in SuS