MRI assessment of cervical spinal cord cross-sectional area in patients with multiple sclerosis.

Objectives: Spinal cord abnormalities including cervical cord atrophy are common in multiple sclerosis (MS). This study aimed to assess the cervical spinal cord cross-sectional area (CSA) using magnetic resonance imaging (MRI) in MS patients. Materials and Methods: Sixty participants were enrolled in this study (16 male and 44 female), 30 patients with MS, diagnosed according to the revised McDonald criteria, and 30 apparently healthy individuals as the control group. CSA of the spinal cord was measured on axial T2-weighted images of the cervical MRI studies from C2 to C7 vertebral levels. Results: There was a significant difference between MS patients and the control group in mean CSA at a different level. The mean CSA at C2, in MS cases, was significantly lower than controls (67.7 ± 9.4 mm2 vs. 81.3 ± 4.6 mm2). Similarly, the mean CSA at C7 (64.4 ± 9.9 mm2) and average C2-7 (68 ± 9.1 mm2) of MS cases were significantly lower than the control. There was a strong inverse correlation between mean cervical cord CSA and duration of the disease and disability score. The reduction in cervical cord CSA was more prominent in patients with secondary progressive MS. There was no significant difference regarding age, gender, type of treatment, or the number of cervical cord lesions. Conclusion: The mean CSA was significantly lower in patients with MS than in the control group and was lesser in progressive types. Patients with a longer duration of MS and a high disability score tend to have smaller CSA.

Epidemiology of multiple sclerosis in Iraq: retrospective review of 4355 cases and literature review.

OBJECTIVES: Multiple sclerosis (MS) is a progressive demyelinating and degenerative disease of the CNS, which is highly variable geographically. The objectives are to establish comprehensive nationwide MS epidemiological data and compare it with similar studies conducted in regional and international communities. To the best of our knowledge, this is the first nationwide comprehensive epidemiological study conducted in Iraq. METHODS: This retrospective study is including 4355 MS cases from the 10 officially authorized MS clinics in Iraq from January 2000 to December 2018. All cases were diagnosed according to McDonald's criteria 2010, new cases diagnosed according to the new criteria of McDonald's criteria 2018. All patients' records were reviewed by the scientific committee. RESULTS: Our study found that 68.51% of MS were females with female-to-male ratio 2.18:1 and 4.07% of patients were diagnosed before they reached 18 years of age. The mean age was 32.3 ± 9.8. The prevalence was found to be 11.73/100,000; it was 16.2/100,000 among females and 7.3/100,000 among males. The incidence was 0.05 in the year 2000 and 1.5 in the year 2017. Initial symptoms were visual 32.06%, motor 28.11%, and 25.58% were sensory symptoms, and 89.97% of the clinical form was relapsing/remitting MS (RRMS) and 81.65% of patients were on first-line treatment. Meanwhile, 66.97% of cases were diagnosed within weeks or months from symptom onset. Summer had the most frequencies regarding birth season. CONCLUSIONS: MS has a significantly increased incidence in Iraq, while prevalence is low compared to neighboring countries. RRMS was the most common clinical form and visual symptoms showed the highest frequency of the first presenting symptoms.

Fatal Case of COVID-19 Pneumonia Associated with Acute Myelopathy.

In December 2019, a novel coronavirus outbreak with multiple system involvement started initially in Wuhan City, Hubei Province of China. Coronavirus disease 2019 (COVID-19) infection is a systemic disorder typically presenting with fever, fatigue, and upper and lower respiratory symptoms, although neurological manifestations are increasingly reported, but pathological mechanisms have yet to be established. The symptoms of infection with COVID-19 are dependent on the patient's age and underlying medical illness, and on the condition of the immune system. Neurotropic and neuroinvasive capabilities of coronaviruses have been described in humans. We herein report a patient infected with COVID-19 who developed pneumonia associated with acute progressive myelopathy. Neurological examination revealed progressive flaccid areflexic paralysis of lower limbs over 3 days with retention of urine and sensory level at 10th spinal thoracic segment (T10). The patient had a positive nasopharyngeal swab for COVID-19 at the onset of the neurological symptoms. This case of acute progressive myelopathy adds further evidence of the complications of severe COVID-19 infection, and we are dealing with a virus of unpredictable behavior. Since this virus neurotropism is not clear yet, further investigations should be conducted on the mechanism of possible neurological infection in patients with COVID-19.

Relation of metabolic syndrome components to left ventricular mass in Mexican Americans versus non-Hispanic whites.

Metabolic syndrome (MetS) is associated with increased risk for cardiovascular disease (CVD). Mexican Americans (MA) exhibit increases in CVD risk factors compared with non-Hispanic whites (NHW), but few data exist comparing the relation of MetS to subclinical CVD, for example, left ventricular (LV) mass. Asymptomatic subjects (104 MA and 101 NHW, 52.2% female, aged 48 ± 12 years) were studied by echocardiography (echo) and by blood and urine tests. Metabolic syndrome was defined based on the American Heart Association/National Heart, Lung, and Blood Institute definition. Echo LV mass was compared with the presence or absence of MetS and with the number of MetS components. Multiple linear regression also examined the association of MetS with LV mass adjusted for non-MetS risk factors. Left ventricular mass was lower in MA (145.5 ± 43.9 g) compared with NHW (160.2 ± 49.9 g) (P < .05), although this difference was attenuated after adjusting for MetS and other risk factors. Left ventricular mass was higher in those with vs without MetS in both MA and NHW men and women (P < .05 to P < .01). There was a significant (P < .001) graded increase in echo LV mass with increasing number of MetS components both in MA (108.3 to 153.8 g) and NHW (144.3 to 215.1 g). In multiple regression analysis, male sex and MetS remained independently associated (P < .0001) with LV mass; however, body mass index explained much of this association, indicating the strong association of obesity with LV mass. Mean LV mass in both MA and NHW adults was higher in those with vs without MetS and with increasing number of MetS components, with body mass index the principal component of MetS associated with LV mass. The prognostic significance of LV mass in persons with MetS requires further study.

Do differences in subclinical cardiovascular disease in mexican americans versus European americans help explain the Hispanic paradox?

Mexican Americans have exhibited increases in various coronary heart disease risk factors compared to European Americans but have also had reportedly lower coronary heart disease mortality from vital statistics studies. We hypothesized this apparent paradox might relate to lower levels of subclinical disease in Mexican Americans. A total of 105 adult Mexican Americans (42 men and 63 women, age 46 +/- 14 years) and 100 European Americans (59 men and 41 women, age 50 +/- 11 years) were studied using blood tests, transthoracic echocardiography, and computed tomography coronary artery calcium (CAC) scans. Despite a greater body mass index and triglycerides in Mexican Americans (p <0.001), the Mexican Americans demonstrated less subclinical disease than did the European Americans (14.4% vs 25.7% with CAC scores >0, p <0.05 and mean left ventricular mass [LV] of 146 vs 160 g, p <0.05). Also, the LV mass was significantly greater in Mexican Americans with than in those without CAC (mean 172 vs 140 g, p <0.05). On logistic regression analysis, age and diastolic blood pressure were associated with an increased likelihood of CAC (p <0.001 and p <0.01, respectively), and Mexican-American ethnicity was associated with a decreased likelihood of CAC (odds ratio 0.33, 95% confidence interval 0.12 to 0.87, p <0.05). On multiple regression analysis, male gender, body surface area, and systolic blood pressure were independently associated with an increased LV mass (all p <0.001). The body mass index was less strongly related to the LV mass than was the body surface area and was not related to CAC. In conclusion, Mexican-American ethnicity is associated with both a lower LV mass and a lower prevalence of CAC, although the differences in LV mass did not remain after adjustment for other factors. Although systolic blood pressure, body surface area, and male gender were most strongly associated with the LV mass, age and diastolic blood pressure, in addition to Mexican-American ethnicity, were the most important indicators of CAC.

Endothelial function and urine albumin levels among asymptomatic Mexican-Americans and non-Hispanic whites.

BACKGROUND: Mexican-Americans (MA) exhibit increases in various cardiovascular disease (CVD) risk factors compared to non-Hispanic Whites (NHW), yet are reported to have lower CVD mortality rates. Our aim was to help explain this apparent paradox by evaluating endothelial function and urine albumin levels in MA and NHW. METHODS: One hundred-five MA and 100 NHW adults were studied by brachial artery flow-mediated dilatation (FMD), blood and urine tests. Participants were studied by ultrasound-determined brachial artery flow-mediated dilatation (FMD), blood and urine tests, at a single visit. RESULTS: Despite higher BMI and triglycerides in MA, MA demonstrated higher FMD than did NHW (9.1 +/- 7.3% vs. 7.1 +/- 6.3%, p < 0.04). Among MA, urinary albumin was consistently lower in participants with FMD >or= 7% FMD versus < 7% FMD (p < 0.006). In multivariate analyses in MA men, urinary albumin was inversely related to FMD (r = -0.26, p < 0.05), as were BMI and systolic blood pressure. In MA women, urinary albumin:creatinine ratio was an independent inverse predictor of FMD (p < 0.05 ). CONCLUSION: To our knowledge, this is the first study to analyze, in asymptomatic adults, the relation of MA and NHW ethnicity to FMD and urine albumin levels. The findings confirm ethnic differences in these important subclinical CVD measures.

Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p <0.001). Long-term supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p <0.001). The improved availability of protein and high-energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p <0.001). In line with these findings, we observed that, after 6 hours of rest following exhaustive swimming, the recovery in mitochondrial ATP content was approximately 70% in adult control rats, approximately 60% in senescent control rats, and normalized in treated rats as compared with animals of the same age unexposed to maximal exertion (p <0.001). In conclusion, nutritional supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing functional performance and accelerating high-energy phosphate recovery after exhaustive exertion.

Amino acid supplementation differentially modulates STAT1 and STAT3 activation in the myocardium exposed to ischemia/reperfusion injury.

We have previously demonstrated that the transcription factor STAT1 plays a critical role in promoting apoptotic cell death, whereas the related STAT3 family member may antagonize STAT1 and protect cardiac myocytes from ischemia/reperfusion (I/R) injury. More recently we demonstrated that long-term nutritional supplementation with mixed amino acids (AAs) can enhance myocyte survival by preserving mitochondrial functional capacity during I/R injury. We therefore investigated whether short-term nutritional supplementation with the same AA mixture has any effects on STAT1 or STAT3 activation in the Langendorff perfused rat heart exposed to I/R injury. In Sprague-Dawley rats given a single oral dose of a mixture of mainly essential l-AA (1 g/kg), and exposed, after 6 hours, to 35 minutes of ischemia, followed by 120 minutes of reperfusion, AA supplementation prolonged STAT3 activation/phosphorylation, while STAT1 activation was reduced. Enhanced STAT3 phosphorylation paralleled a reduction in expression of Fas, a known STAT1 target gene and proapoptotic marker that is upregulated after I/R. Moreover, abrogation of STAT3 activation by means of the JAK inhibitor AG490, reduced, but did not abolish, the cardioprotective effects of AA supplementation after I/R. These results show that modulation of the functional balance between STAT3 and STAT1, with preferential activation of prosurvival STAT3 over the proapoptotic STAT1, represents a mechanism by means of which short-term oral supplementation with mixed AAs protects the heart from I/R injury.

The effect of freezing and long-term storage on the stability of cardiac troponin T.

Cardiac troponin T (cTnT) levels are widely used to assess for evidence of myocardial infarction. We studied the effect of freezing and long-term storage on the stability of cTnT in blood samples from 178 patients with end-stage renal failure. The serum was separated and divided into multiple aliquots. Baseline cTnT levels were measured in the unfrozen aliquots. The remaining aliquots were frozen using standard techniques. The aliquots were thawed after 3, 6, 12, or 24 months and cTnT levels measured. There were no significant changes in the mean +/- SEM cTnT levels up to 12 months (0.111 +/- 0.098 microg/L) compared with baseline (0.114 +/- 0.098 microg/L); after 24 months, cTnT levels were significantly lower (0.107 +/- 0.095 microg/L) than baseline ( P = .004). The cTnT assay is a reliable method of measuring the cTnT level in human serum up to 12 months of frozen storage. However, after 24 months, the cTnT level was 0.007 microg/L lower than baseline, potentially causing erroneous interpretations. The clinical significance of the change in the cTnT level after long-term frozen storage is unclear. Further studies, including prospective analysis of patient outcomes, should be helpful.

Technical aspects of diastology: why mitral inflow and tissue Doppler imaging are the preferred parameters?

Doppler methods for assessing left ventricular (LV) diastolic function have increased in number and complexity. However, time constraints may prevent measurement of all parameters during routine transthoracic echocardiography. Therefore, we designed a study to determine which Doppler parameters could be most successfully and quickly obtained. The recording success rate and time required to record different LV diastolic function parameters were evaluated in 80 patients. A specific recording protocol was followed by an experienced, credentialed sonographer and time intervals to record each parameter were measured. In comparison with color Doppler M-mode of LV inflow propagation velocities (Vp) and pulmonary venous (PV) flow measurements, transmitral valve (MV) flow and tissue Doppler imaging (TDI) of the mitral annulus had the highest recording success rate and required the shortest time to record. PV flow and Vp took longer to obtain (80.1+/-34.3 sec and 57.1+/-29.1 sec, respectively) than did mitral valve inflow (36.3+/-20.7 sec) and mitral valve annular TDI (29.3+/-18.4 sec for septal and 33.3+/-14.5 sec for lateral). MV flow velocities, Vp, and TDI were successfully recorded in virtually all patients (99-100%). In comparison, the PV flow velocities and durations were successfully recorded less often. The range of success rates for the six PV flow parameters was 49-84%. Since MV flow and TDI also have been shown by us to have the lowest interreader variability, measurement of these two parameters may be preferred for routine clinical evaluation of LV diastolic function in a busy echocardiography laboratory.

A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins.

Ephedra, a herb reported to suppress appetite and stimulate the sympathetic nervous system as well as cardiac performance, has recently been related to several adverse events, including seizure, stroke, hypertension, myocardial infarction, and sudden death. Here, we describe the case of a 45-year-old woman who died of cardiovascular collapse while taking ephedra. Tissue analysis revealed non-specific degenerative alterations in the myocardium (lipofuscin accumulation, basophilic degeneration and vacuolation of myocytes, as well as myofibrillary loss), associated with myocyte apoptosis, caspase activation, and extensive cleavage of miofibrillary proteins alpha-actin, alpha-actinin, and cardiac troponin T. Healthcare professionals are therefore urged to warn their patients about the risk of serious adverse effects, which may follow ephedra intake.

Glutathione S-transferase overexpression protects against anthracycline-induced H9C2 cell death.

Anthracyclines (AC) are antitumor antibiotics with significant activity against solid and hematologic malignancies. One problem preventing more widespread use has been the development of cardiac toxicity. Experimental evidence supports oxidant stress as an important trigger and/or mediator of AC-induced cardiotoxicity (ACT). Therefore, reducing oxidant stress should be protective against ACT. To determine whether antioxidant protein overexpression can reduce ACT, we developed a cell culture model system using the H9C2 cardiac cell line exhibiting controlled overexpression of the alpha(4)-isoform of glutathione-S-transferase (GST). Treatment with the AC doxorubicin (DOX) produced both oncosis, manifested by an increase in the number of cells staining positive for Trypan blue, and apoptosis, indicated by the presence of positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. In both cases, the loss of cell viability was preceded by an AC-induced increase in fluorescence with carboxy-2',7'-dichlorofluorescein diacetate, demonstrating the presence of high levels of reactive oxygen species (ROS). The DOX-induced increase in ROS was reduced to control levels by maximal GST overexpression. Coincident with this elimination of oxidative stress, there was a reduction in both Trypan blue and TUNEL-positive cells, indicating that GST overexpression reduced both ROS and cell death in this model system. We conclude that GST overexpression may be an important part of a protective strategy against ACT and that this model system will aid in defining steps in the pathway(s) leading to AC-induced cell death that can be therapeutically manipulated.