Minimal Manifestations Research Articles

A comparative experimental-morphological study of the methods of chemodestruction, cryodestruction and laser destruction of the peripheral nerve trunk

An experimental morphological study of the methods of chemodestruction, cryodestruction and laser destruction as those of medical denervation in pharmacoresistant forms of prosopalgia was carried out. The obtained data testify to the presence of evident destructive macro- and microscopic changes both in the nerve trunk and its surrounding tissues when using alcoholic chemodestruction. A lesser degree of morphological changes was observed in phenol chemodestruction. Cryodestruction was characterized by morphological signs of persistent denervation with a minimal manifestation of perifocal changes in the surrounding tissues. The laser method of denervation resulted in replacement of destruction by regeneration in the early period. Perifocal changes were minimal.

CHRONIC ACTINIC DERMATITIS AND PATHOLOGY OF THE DIGESTIVE TRACT

Chronic actinic dermatitis (CAD) is characterized by itchy eczematous lesions on areas of skin exposed to sunlight. The disease affects men middle-aged and elderly. Three criteria was taken into account to diagnose CAD: the effects of the minimum erythemal doses of UVA and UVB, a persistent eczematous lesions in areas exposed to radiation and sometimes non-irradiated sites, and histopathological changes resembling chronic eczema. The eczematous process of the skin develops as a result of a number of factors that lead to sensitization of the organism, including in the pathology of the digestive tract and the hepatobiliary system. A correlation was found between the severity of eczematous skin lesions and the severity of the digestive tract disease. Material and methods. Under the care of the Department of dermatology and venereology Clinics of the Samara state medical University of Minzdrav of Russia were 65 men with CAD, among them 61 (93.9%) patients are over 40 years old. The pathology of the digestive tract and the hepatobiliary system was detected in 51 (78.6%) patients. Concomitant diseases of the digestive tract and the hepatobiliary system had a latent period and were identified for the first time due to a comprehensive survey in 37 (57%) patients. Results. In most cases, CAD on the background of the digestive system disease, there was a moderate and severe course of the eczematous process. The frequency of occurrence of reflux esophagitis, superficial and atrophic gastritis, duodenogastric reflux, as well as the combined pathology of the hepatobiliary system was maximal in patients with the most severe course of the eczematous process. The majority of patients without pathology of the digestive tract and hepatobiliary system had minimal skin manifestations of eczema.

Oral corticosteroid dosing regimen and long-term prognosis in generalised myasthenia gravis: a multicentre cross-sectional study in Japan

ObjectiveWe examined the correlation between the dosing regimen of oral prednisolone (PSL) and the achievement of minimal manifestation status or better on PSL ≤5 mg/day lasting >6 months (the treatment...

Different neurologic outcomes of myasthenia gravis with thymic hyperplasia and thymoma after extended thymectomy: A single center experience

This study aimed to reveal the clinical course and outcomes of myasthenia gravis (MG) in patients with thymic lymphoid hyperplasia and thymoma undergoing extended thymectomy and to identify the clinical prognostic factors of remission for MG. In total, 73 patients undergoing extended thymectomy were divided into two groups: group A with lymphoid hyperplasia (n=39) and group B with thymoma (n=34). According to the MG Foundation of America (MGFA) post-intervention status, the primary endpoint was a composite measure defined as achievement of complete stable remission (CSR), pharmacologic remission (PR), minimal manifestations (MM) or improvement (IM). The secondary endpoint was CSR. The cumulative probabilities of reaching the primary endpoint were 71.8% in group A and 85.3% in group B (p=0.164), respectively. Using Kaplan-Meier survival analysis, the probability of reaching the primary endpoint in group B was remarkably greater than group A (p=0.036). Cox multivariate analysis indicated that pre-operative MGFA class I (HR: 3.019, 95% CI: 1.084–8.410) and MGFA II (2.665, 95% CI: 1.033–6.873) compared to MGFA III and presence of thymoma (HR: 2.229, 95% CI: 1.079–4.606), showed the most consistent association with remission of MG after thymectomy. Finally, thymic lymphoid hyperplasia and severe symptoms may negatively affect prognosis of MG following thymectomy.

THE EFFECTIVENESS OF COMBINED TREATMENT OF DISSEMINATED MALIGNANT PLEURAL MESOTHELIOMA, A DESCRIPTION OF THE CLINICAL CASE

Modern approach to the individualization of the management of patients based on the careful observation for the minimal manifestations of the disease, prescription of pemetrexed at the first line of therapy, combination with platinum preparations and antiangiogenic targeted preparation bevazisumab allows control the disease at the advanced stage of pleural mezoteliom and support the good active state of patients during the long time.

Early fast-acting treatment strategy against generalized myasthenia gravis

Introduction In this study we sought to clarify the effects of early fast-acting treatment (EFT) strategies on the time course for achieving the treatment target in generalized myasthenia gravis (MG). Methods This retrospective study of 923 consecutive MG patients analyzed 688 generalized MG patients who had received immunotherapy during the disease course. The time to first achieve minimal manifestations (MM) or better while receiving prednisolone at ≤5 mg/day for ≥6 months (MM-or-better-5mg) up to 120 months after starting immunotherapy was compared between EFT and non-EFT patients. Results Achievement of MM-or-better-5mg was more frequent and earlier in the EFT group (P = 0.0004, Wilcoxon test; P = 0.0001, log-rank test). Multivariate Cox regression analysis calculated a hazard ratio of 1.98 (P < 0.0001) for utilization of EFT. Dosing regimens of oral steroids in EFT produced no differences in the time course. Conclusions EFT strategies are advantageous for early achievement of MM-or-better-5mg. Muscle Nerve 55: 794–801, 2017

Комплексная оценка диагностических критериев у женщин с цистоцеле и стрессовым недержанием мочи

The purpose of the study: clarification of absolute and relative criteria for the operative treatment of prolapse of the pelvic organs (POP) and stress urinary incontinence (SUI). Patients and methods. 85 patients with POP and SUI were observed. These women were divided into groups according to the stage of POP and SUI: group 2 – 32 patients with I and II stages of POP and SUI 2a, 2b types of light and moderate severity; group 3 (main) – 53 patients with III and IV stages of POP and SUI type 3 moderate and severe severity. This group of patients subsequently undergone operative treatment according to the patent for utility model No. 109201. The main group (3rd group) included: 3a group – 28 women with III and IV stages of POP and SUI type 3 moderate and severe severity without delay in urination; 3b group – 25 women with III and IV stages of POP and SUI type 3 moderate and severe severity with delay of urination (chronic or acute). 15 women were examined without complaints, who entered the control group (1st group). Results. According to the results of the study, it was recorded that, regardless of the stage of the POP and SUI, even it’s minimal manifestation significantly reduces the quality of life of patients (by 64%) due to the impact on the physical, but greater, on the psychological components of health. Conclusion. The absolute criterion for operative treatment is a set of prolapse of the pelvic organs (POP), urinary incontinence, vesicularization of the bladder type 2a and above, an increase of the posterior urethro-vascular angle of more than 114°. Treatment of stress urinary incontinence on the background of POP should necessarily include fixation of the uterine ligaments and the Berch surgery because of significant deformation of the bladder neck. Key words: pelvic organ prolapse, urinary incontinence, methods of diagnostics.

Usefulness of Adenosine Testing in the Differential Diagnosis Between Fasciculoventricular Pathways and Wolff-Parkinson-White-type Ventricular Preexcitation

Background: The diagnosis of Wolff-Parkinson-White-type ventricular preexcitation on the surface electrocardiogram is generally easy. However, in patients with minimal or subtle electrocardiographic manifestations, the differential diagnosis with other types of preexcitation, as fasciculoventricular fibers, may be difficult. Adenosine testing is a useful tool for that purpose. Objective: The aim of this study is to describe our experience with adenosine testing in the differential diagnosis of patients with minimal ventricular preexcitation. Methods: Of 313 consecutive patients with diagnosis of Wolff-Parkinson-White, 28 patients with minimal preexcitation on the electrocardiogram that questioned the diagnosis were analyzed. Results: Adenosine testing produced transient first degree, second degree and complete atrioventricular block without changing the ventricular activation pattern, ruling out Wolff-Parkinson-White syndrome. Twenty patients underwent an electrophysiologic study which confirmed the diagnosis of fasciculoventricular pathways in 16 cases. Conclusion: In patients with suspected Wolff-Parkinson-White ventricular preexcitation, adenosine testing proved to be an efficient and safe tool to establish or rule out the diagnosis.

Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan.

To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 ± 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

Rituximab as treatment for anti-MuSK myasthenia gravis: Multicenter blinded prospective review.

To evaluate the efficacy of rituximab in treatment of anti-muscle-specific kinase (MuSK) myasthenia gravis (MG). This was a multicenter, blinded, prospective review, comparing anti-MuSK-positive patients with MG treated with rituximab to those not treated with rituximab. The primary clinical endpoint was the Myasthenia Gravis Status and Treatment Intensity (MGSTI), a novel outcome that combines the Myasthenia Gravis Foundation of America (MGFA) postintervention status (PIS) and the number and dosages of other immunosuppressant therapies used. A priori, an MGSTI of level ≤2 was used to define a favorable outcome. Secondary outcomes included modified MGFA PIS of minimal manifestations or better, mean/median prednisone dose, and mean/median doses of other immunosuppressant drugs. Seventy-seven of 119 patients with anti-MuSK MG evaluated between January 1, 2005, and January 1, 2015, at 10 neuromuscular centers were selected for analysis after review of limited clinical data by a blinded expert panel. An additional 22 patients were excluded due to insufficient follow-up. Baseline characteristics were similar between the rituximab-treated patients (n = 24) and the controls (n = 31). Median follow-up duration was >3.5 years. At last visit, 58% (14/24) of rituximab-treated patients reached the primary outcome compared to 16% (5/31) of controls (p = 0.002). Number needed to treat for the primary outcome is 2.4. At last visit, 29% of rituximab-treated patients were taking prednisone (mean dose 4.5 mg/day) compared to 74% of controls (mean dose 13 mg/day) (p = 0.001 and p = 0.005). This study provides Class IV evidence that for patients with anti-MuSK MG, rituximab increased the probability of a favorable outcome.

Prompt Response to Prednisone Predicts Benign Course in MuSK-MG

Background: The difficult course of patients with myasthenia gravis (MG) with anti-muscle-specific tyrosine kinase antibodies (MuSK) has been emphasized. However, no clear information is available on patients who have a benign course. Methods: This study was aimed at comparing patients with favorable (minimal manifestations [MM] or better) and unfavorable outcomes to determine whether excellent response to corticosteroid (CS) treatment within 3 months (good response-3 months) has any predictive effect on the prognosis. Results: Forty-six percent of 46 patients had a favorable outcome at year 3 and 54% at final follow-up. The major finding of this study was its high predictive value with good response-3 months. Those with good response-3 months had significantly more favorable outcome as compared to those without at year 3. The positive predictive value of good response-3 months was high (89% at year 3 and 84% at final follow-up). The negative predictive value diminished from 85% at year 3 to 67% at final follow-up due to increasing number of patients improving in the long run. Overall, 33% of the patients had a benign course with good response-3 months and no major exacerbations until the end of follow-up. Conclusions: Excellent response to CSs within 3 months appears to predict a favorable outcome in MuSK-MG.

Factors affecting outcome in ocular myasthenia gravis

ABSTRACTAim of the study: 50%–60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables.Materials and methods: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients.Results: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL.Conclusions: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.

Improving urban visibility through fractal analysis of street edges: The case of John Evans Atta Mills High Street in Accra, Ghana

Streets are a representation of cities, and the image of a city is a reflection of its home country. Although attempts to ensure harmonious spatial and environmental development in Ghanaian settlements date back to the colonial era, these efforts have minimal physical manifestation in the urban fabric of the city of Accra. The Independence Arch of Ghana, an important landmark in the urban fabric and history of Accra, lacks the striking vista and approach it deserves. This paper introduces the use of fractal analysis of street edges to understand the characteristics of the John Evans Atta Mills (JEAM) High Street for developing recommendations to improve visibility along its stretch and the overall image of the city. The box-counting method with visual survey was used in research. The pertinent questions this paper seeks to address are as follows: What factors affect the visibility and imageability of JEAM High Street? What design aspects should be considered to improve urban visibility along JEAM High Street? What is the link of fractals to urban design and architecture? The paper recommends various design considerations and qualities to improve the urban visibility and imageability of JEAM High Street.

Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

SummaryTuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells. TSC2 astrocytes had increased saturation density and higher proliferative activity. Moreover, the activity of the mTOR pathway was enhanced in pNSCs and induced in neurons and astrocytes. Thus, our results suggested that TSC2 heterozygosity caused neurological malformations in pNSCs, indicating that its heterozygosity might be sufficient for the development of neurological abnormalities in patients.

Rituximab treatment of myasthenia gravis: A systematic review

Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P < 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20+ B-cells were observed up to 20 and 16 weeks, respectively, after 4 weekly infusions. Muscle Nerve 56: 185-196, 2017.

Clinical case of ventricular septal rupture in patient with acute myocardial infarction

This article describes ventricular septal rupture in the acute phase of myocardial infarction after thrombolytic therapy. The peculiarity of this case is the lack of patient expressed pain and minimal manifestations of heart failure on the background specific to ventricular septal rupture ECG changes and echocardiographic data. To analyze the main factors giving the opportunity to assess the risk of this complication in patients with acute myocardial infarction. The clinical case demonstrates the success of the conservative management of patient with acute myocardial infarction complicated by early ventricular septal rupture.

Early fast-acting treatment strategy against generalized myasthenia gravis.

ABSTRACTIntroductionIn this study we sought to clarify the effects of early fast‐acting treatment (EFT) strategies on the time course for achieving the treatment target in generalized myasthenia gravis (MG).MethodsThis retrospective study of 923 consecutive MG patients analyzed 688 generalized MG patients who had received immunotherapy during the disease course. The time to first achieve minimal manifestations (MM) or better while receiving prednisolone at ≤5 mg/day for ≥6 months (MM‐or‐better‐5mg) up to 120 months after starting immunotherapy was compared between EFT and non‐EFT patients.ResultsAchievement of MM‐or‐better‐5mg was more frequent and earlier in the EFT group (P = 0.0004, Wilcoxon test; P = 0.0001, log‐rank test). Multivariate Cox regression analysis calculated a hazard ratio of 1.98 (P < 0.0001) for utilization of EFT. Dosing regimens of oral steroids in EFT produced no differences in the time course.ConclusionsEFT strategies are advantageous for early achievement of MM‐or‐better‐5mg. Muscle Nerve 55: 794–801, 2017

Social disadvantages associated with myasthenia gravis and its treatment: a multicentre cross-sectional study

ObjectivesTo clarify the social disadvantages associated with myasthenia gravis (MG) and examine associations with its disease and treatment.DesignCross-sectional study.Setting and participantsWe evaluated 917 consecutive cases of established MG seen at...

Author response: International consensus guidance for management of myasthenia gravis: Executive summary.

We appreciate the comments of Li et al. on our article.1 The 2000 Myasthenia Gravis Foundation of America Task Force definition of minimal manifestations included the statement “This class recognizes that some patients who otherwise meet the definition of CSR or PR do have weakness that is only detectable by careful examination.”2 In our article, we noted that “Clinical examination is assumed to have been performed by physicians skilled in the evaluation of neuromuscular disease.”1 Thus, only weakness that is not clinically important would be acceptable under our definition of MMS.

Letter re: International consensus guidance for management of myasthenia gravis: Executive summary.

In the international consensus for managing myasthenia gravis (MG), minimal manifestation status (MMS) or better was recommended as the treatment goal.1 MMS refers to no symptoms of functional limitations from MG, but some weakness on examination of some muscles.2 However, there are no criteria to detect the minimal weakness that is clinically important and biologically plausible. Only one study tried to link MMS and MG-specific quality of life scores.3 Moreover, the dose of pyridostigmine is an important factor that should be considered in attributing symptoms or functional limitations to MG. What is the optimal cutoff on measurements of weakness and pyridostigmine dose in the definition of MMS?