Cases Of Sclerosis Research Articles

Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NAD+ balance as a therapeutic strategy

Mitochondrial defects result in dysregulation of metabolomics and energy homeostasis that are detected in upper motor neurons (UMNs) with TDP-43 pathology, a pathology that is predominantly present in both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). While same mitochondrial problems are present in the UMNs of ALS patients with TDP-43 pathology and UMNs of TDP-43 mouse models, and since pathologies are shared at a cellular level, regardless of species, we first analyzed the metabolite profile of both healthy and diseased motor cortex to investigate whether metabolomic changes occur with respect to TDP-43 pathology. High-performance liquid chromatography, high-resolution mass spectrometry and tandem mass spectrometry (HPLC–MS/MS) for metabolite profiling began to suggest that reduced levels of NAD+ is one of the underlying causes of metabolomic problems. Since nicotinamide mononucleotide (NMN) was reported to restore NAD+ levels, we next investigated whether NMN treatment would improve the health of diseased corticospinal motor neurons (CSMN, a.k.a. UMN in mice). prpTDP-43A315T-UeGFP mice, the CSMN reporter line with TDP-43 pathology, allowed cell-type specific responses of CSMN to NMN treatment to be assessed in vitro. Our results show that metabolomic defects occur early in ALS motor cortex and establishing NAD+ balance could offer therapeutic benefit to UMNs with TDP-43 pathology.

PiRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis

The pathological hallmark of the majority of amyotrophic lateral sclerosis (ALS) cases is the mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43), an RNA-binding protein. Several studies have attributed disease processes of ALS to abnormal RNA metabolism. However, dysregulated biogenesis of RNA, especially non-coding RNA (ncRNA), is poorly understood. To resolve it, RNA-Seq, biochemical, and immunohistochemical analyses were performed on the pyramidal tract of the medulla oblongata of sporadic ALS (sALS) and control postmortem brain samples. Here, we report perturbation of ncRNA biogenesis in PIWI-interacting RNA (piRNA) in several sALS brain samples associated with TDP-43 pathology. In addition, we confirmed the dysregulation of two PIWI homologs, PIWI-like-mediated gene silencing 1 (PIWIL1) and PIWIL4, which bind to piRNAs to regulate their expression. PIWIL1 was mislocalized and co-localized with TDP-43 in motor neurons of sporadic ALS lumbar cords. Our results imply that dysregulation of piRNA, PIWIL1, and PIWIL4 is linked to pathogenesis of ALS. Based on these results, piRNAs and PIWI proteins are potential diagnostic biomarkers and therapeutic targets of ALS.

A Rare Case of Tuberous Sclerosis with Adenocarcinoma of Stomach

A Rare Case of Tuberous Sclerosis with Adenocarcinoma of Stomach

Mesangial sclerosis in a patient with type 1 diabetes following simultaneous pancreas-kidney transplantation despite maintenance of normoglycemia: a case report

BackgroundSimultaneous pancreas-kidney transplantation is considered a curative treatment for type 1 diabetes complicated by end-stage kidney disease. We report herein a case of mesangial sclerosis in a patient who underwent successful kidney-pancreas transplantation despite well-controlled glucose and excellent pancreatic allograft function.Case presentationA 76-year-old type 1 diabetic man who underwent a simultaneous pancreas-kidney transplantation 19 years prior presented with persistent nephrotic range proteinuria although creatinine was at his baseline (normal) level. Hemoglobin A1c and fasting glucose were well controlled without the use of insulin or oral antihyperglycemic agents. Serum lipase and amylase were within the reference range and there was no evidence of donor-specific antibodies. Kidney allograft biopsy was performed to evaluate proteinuria and showed diffuse capillary loop thickening and diffuse moderate to severe mesangial sclerosis resembling diabetic nephropathy.ConclusionsThis case demonstrates a case of mesangial sclerosis resembling diabetic nephropathy in a patient with good glucose control after simultaneous pancreas-kidney transplantation with excellent pancreatic allograft function.

Acute retinal necrosis caused by co-infection with multiple viruses in a natalizumab-treated patient: a case report and brief review of literature

BackgroundAcute retinal necrosis is considered a rare infectious uveitis. This condition is usually caused by varicella-zoster virus or herpes simplex virus. Acute retinal necrosis caused by co-infection with multiple viruses is extremely rare. Herein, we report a case of acute retinal necrosis caused by co-infection with herpes simplex virus (type I and II) and varicella-zoster virus (VZV) in a natalizumab-treated patient due to multiple sclerosis.Case presentationAn adult man presented with a complaint of decreased vision of the right eye from 12 days ago. He was a known case of multiple sclerosis receiving natalizumab. Examination of the right eye revealed severe conjunctival injection, fine diffuse keratic precipitates, 3 + anterior chamber and vitreous cells, elevated intraocular pressure (26 mmHg), a blurred optic disk with hemorrhagic patches, and occlusive vasculitis plus confluent necrotizing patches in the peripheral retina compatible with diagnosis of acute retinal necrosis. He underwent anterior chamber and vitreous tap, and real-time PCR detected HSV I & II and VZV on the vitreous specimen. A second PCR showed the same result. After neurological consultation, natalizumab was discontinued and intravenous acyclovir was started followed by oral acyclovir and oral prednisolone to control the disease, which was successful.ConclusionsAlthough rare, multiple-viral infection should be considered in the physiopathology of acute retinal necrosis, especially in immunosuppressed patients.

Protein disulphide isomerase (PDI) is protective against amyotrophic lateral sclerosis (ALS)-related mutant Fused in Sarcoma (FUS) in in vitro models

Mutations in Fused in Sarcoma (FUS) are present in familial and sporadic cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). FUS is localised in the nucleus where it has important functions in DNA repair. However, in ALS/FTD, mutant FUS mislocalises from the nucleus to the cytoplasm where it forms inclusions, a key pathological hallmark of neurodegeneration. Mutant FUS also inhibits protein import into the nucleus, resulting in defects in nucleocytoplasmic transport. Fragmentation of the neuronal Golgi apparatus, induction of endoplasmic reticulum (ER) stress, and inhibition of ER-Golgi trafficking are also associated with mutant FUS misfolding in ALS. Protein disulphide isomerase (PDI) is an ER chaperone previously shown to be protective against misfolding associated with mutant superoxide dismutase 1 (SOD1) and TAR DNA-binding protein-43 (TDP-43) in cellular and zebrafish models. However, a protective role against mutant FUS in ALS has not been previously described. In this study, we demonstrate that PDI is protective against mutant FUS. In neuronal cell line and primary cultures, PDI restores defects in nuclear import, prevents the formation of mutant FUS inclusions, inhibits Golgi fragmentation, ER stress, ER-Golgi transport defects, and apoptosis. These findings imply that PDI is a new therapeutic target in FUS-associated ALS.

Medical cannabis and cannabis-based medicine show both potential efficacy and potential harms: Cross-sectional comparison with controls on self-rated and interviewer-rated outcomes within the Danish pilot program on medical cannabis

Background and purposeDenmark launched a pilot program of medical cannabis in January 2018. The aim was to establish whether medical cannabis and cannabis-based medicine (MC/CBM) were superior and safe compared to conventional treatment, regardless of the indications for which people received such medication. Materials and methodsPeople (cases) were identified who had redeemed at least one prescription of MC/CBM according to the nationwide, unselected Danish registers. These were propensity-score matched to controls with the same indications who had not used MC/CBM. Potential participants were contacted electronically, and if willing to participate filled in various survey instruments online. Participants were also interviewed in person in order to investigate symptoms of depression, anxiety, and to assess cognitive levels. Different sets of analyses were conducted, handling potential confounders in different ways. ResultsIn the primary analyses, cases were more satisfied with their treatment than were controls (mean (SD) 29.2 (4.8) versus 26.5 (4.5) on the CSQ, p = 0.006), and scored lower on depression (3.3 (3.0) versus 4.6 (2.9), p = 0.03). Cases reported higher levels of pain than controls when measured on the SF-36 bodily-pain subdomain (36.3 (23.0) versus 48.7 (30.1), p = 0.01). There were indications of worse symptoms of multiple sclerosis in cases compared to controls. Reported side-effects were generally mild. ConclusionBoth potential effects and harms of MC/CBM were observed. Randomized trials are required to establish if these are true effects and harms, or due to confounding by indication.

Erasmus syndrome presented as CREST syndrome with Scl-70 positivity: a case report

Erasmus syndrome is a rare pathology defined as a systemic sclerosis secondary to contact with silica, associated or not with silicosis. More recent studies have related silica as an environmental factor stimulating different immune responses of the body. This report was made with the objective of presenting a rare case of systemic sclerosis, in a localized cutaneous form, also called CREST syndrome. A patient with a 20-year history of mining developed silicosis, cutaneous calcinosis, Raynauld's phenomenon, esophagopathy, sclerodactyly, telangiectasias and high positivity for the antitopoisomerase I antibody, the most common antibody in the systemic form.

Outpatient healthcare utilization among incident cases of systemic sclerosis: results from a population-based US cohort (1988–2016)

Objective Systemic sclerosis (SSc) is a complex, heterogeneous connective tissue disease with multiorgan dysfunction. This study aimed to compare healthcare utilization among incident cases of SSc versus age- and gender-matched comparators. Method A population-based cohort of physician-diagnosed patients with SSc in Olmsted County, MN, USA, from 1 January 1988 to 31 December 2016 was assembled. A 2:1 cohort of age- and gender-matched non-SSc subjects was randomly selected for comparison. Patients were followed until death, migration from Olmsted County, or 31 December 2017. Outpatient utilization data were obtained beginning 12 months before the SSc incidence/index date and compared using negative binomial and multinomial models. Services were summarized as visit-days to avoid overestimation of services provided. Results The study included 69 incident SSc cases and 138 non-SSc comparators (mean ± sd age 57 ± 16 years at diagnosis/index, 90% female). Patients with SSc had higher utilization of outpatient physician, laboratory, and combined radiology visit-days annually for the year before and for each of the first 5 years after diagnosis than comparators. Among patients with SSc, healthcare utilization was highest during the year of SSc diagnosis. Rate ratios comparing utilization in patients with and without SSc ranged from 1.8 to 3.0 for all comparisons. Conclusion Higher utilization of outpatient physician, laboratory, and radiology visit-days was observed among patients with SSc compared to non-SSc subjects throughout 5 years of disease duration, indicating high and continued care needs in this patient population. The highest utilization of services among SSc patients occurred during the year of SSc diagnosis.

ОСОБЕННОСТИ ДЕТСКОГО РАССЕЯННОГО СКЛЕРОЗА

Background. Demyelinating diseases are one of the most pressing and debatable problems in neurology. Despite the emergence of improved diagnostic criteria and new directions in therapy, multiple sclerosis is a leading cause of disability among young patients. According to epidemiological studies, about 3 million people worldwide suffer from multiple sclerosis. At the same time, from 2.7 to 10.5% of all cases of multiple sclerosis worldwide are observed in children under the age of 18, with a tendency towards an increase in the disease incidence. Purpose. To analyze the results of scientific studies of cases of childhood multiple sclerosis. Material and methods. A qualitative analysis of Russian-language and English-language literature sources containing data on cases of childhood multiple sclerosis has been carried out. Results. It has been established that the incidence of multiple sclerosis among pediatric patients is significantly lower in comparison with the adult population. The clinical picture is polymorphic and, in some cases, atypical. Conclusions. Current understanding of the term "pediatric multiple sclerosis" indicates a narrow window of onset with cognitive decline different from adults, combined with a higher number of relapses and more inflammatory lesions compared to adult multiple sclerosis. The polymorphic clinical picture and atypical manifestations of multiple sclerosis in childhood, as well as the debut in the form of a clinically isolated syndrome, can complicate early differential diagnosis and increase the interval from the onset of the disease to the administration of the necessary pharmacotherapy, which can reduce the severity of the course of the disease, the frequency of relapses and increase the interval "debut - disability".

Amyotrophic Lateral Sclerosis Risk, Family Income, and Fish Consumption Estimates of Mercury and Omega-3 PUFAs in the United States.

Most amyotrophic lateral sclerosis (ALS) cases are considered sporadic, without a known genetic basis, and lifestyle factors are suspected to play an etiologic role. We previously observed increased risk of ALS associated with high nail mercury levels as an exposure biomarker and thus hypothesized that mercury exposure via fish consumption patterns increases ALS risk. Lifestyle surveys were obtained from ALS patients (n = 165) and n = 330 age- and sex-matched controls without ALS enrolled in New Hampshire, Vermont, or Ohio, USA. We estimated their annual intake of mercury and omega-3 polyunsaturated fatty acid (PUFA) via self-reported seafood consumption habits, including species and frequency. In our multivariable model, family income showed a significant positive association with ALS risk (p = 0.0003, adjusted for age, sex, family history, education, and race). Neither the estimated annual mercury nor omega-3 PUFA intakes via seafood were associated with ALS risk. ALS incidence is associated with socioeconomic status; however, consistent with a prior international study, this relationship is not linked to mercury intake estimated via fish or seafood consumption patterns.

Bilateral renal angiomyolipomas in tuberous sclerosis

BackgroundTuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign hamartomas in multiple organs of the body. Renal angiomyolipomas (AML) are commonly associated with TSC. They are mostly asymptomatic. But large and rapidly growing AMLs with the presence of an aneurysm cause symptoms and pose a life-threatening risk for hemorrhage.Case presentationOur patient is a 25-year-old female who presented to us as an undiagnosed case of tuberous sclerosis having a large abdominal mass. She fulfilled the clinical criteria required for the diagnosis of TSC. The CT scan revealed an 18 × 13 × 33 cm fat-containing lesion in the right kidney with an adjacent aneurysm measuring around 16 cm in diameter. Due to the large size of the AML and associated aneurysm, surgical exploration was mandated. On the contralateral kidney, multiple contrast-enhancing soft-tissue densities were present that appeared suspicious on radiology. So a percutaneous biopsy of those lesions was done. Fortunately, it had the same histopathology as an Angiomyolipoma. Nephrectomy of the right-sided kidney with AML has been done. The left-sided lesions that are less than 2 cm and asymptomatic are kept on close surveillance. Any change in size will prompt therapy with mTOR inhibitors.ConclusionWhen dealing with bilateral renal AML, it is important to adopt a conservative approach. When intervention is indicated, the least invasive strategy should be sought and enacted. Radical surgery should be the last resort.

Cyclophosphamide for the treatment of Acute Exacerbation of Interstitial Lung Disease: A Review of the Literature.

Acute exacerbation of interstitial lung disease is a serious and life-threatening event but little is known about its treatment. Cyclophosphamide has been proposed in randomized clinic trials as a treatment option in progressive cases of systemic sclerosis related interstitial lung disease. However, in acute exacerbation of interstitial lung disease, we found only small case series, and retrospective studies, mostly with no comparative groups which described the role of cyclophosphamide. Results of these studies showed mixed outcomes, with no robust evidence that cyclophosphamide adds any benefit in treating acute exacerbations of interstitial lung disease. More well-designed studies including randomized clinical trials are needed to better understand the role of cyclophosphamide during exacerbations of interstitial lung disease. In this review article, we summarize the current evidence on the use of cyclophosphamide in interstitial lung disease with a focus on the acute exacerbation events.

REscan: inferring repeat expansions and structural variation in paired-end short read sequencing data.

MotivationRepeat expansions are an important class of genetic variation in neurological diseases. However, the identification of novel repeat expansions using conventional sequencing methods is a challenge due to their typical lengths relative to short sequence reads and difficulty in producing accurate and unique alignments for repetitive sequence. However, this latter property can be harnessed in paired-end sequencing data to infer the possible locations of repeat expansions and other structural variation.ResultsThis article presents REscan, a command-line utility that infers repeat expansion loci from paired-end short read sequencing data by reporting the proportion of reads orientated towards a locus that do not have an adequately mapped mate. A high REscan statistic relative to a population of data suggests a repeat expansion locus for experimental follow-up. This approach is validated using genome sequence data for 259 cases of amyotrophic lateral sclerosis, of which 24 are positive for a large repeat expansion in C9orf72, showing that REscan statistics readily discriminate repeat expansion carriers from non-carriers.Availabilityand implementationC source code at https://github.com/rlmcl/rescan (GNU General Public Licence v3).

Coexistence of multiple sclerosis and brain tumors: a literature review.

Concurrent development of primary brain tumors and multiple sclerosis is quite rare. Only a few dozens of such comorbidity have been reported. Nevertheless, given the fact that such pathologies are characterized by similar clinical picture and neuroimaging findings, issues about diagnosis and differential diagnosis of such conditions often arise, which makes the problem relevant. A literature review was conducted using PubMed, by selecting articles on concurrent multiple sclerosis and brain tumors, particularly glial origin tumors, over the past 20 years (1989 to 2019). The search was performed in English, Russian, and Ukrainian using the following key words and terms: comorbidity, concomitance, multiple sclerosis, brain tumor, glioma, astrocytoma, glioblastoma. The analysis included all articles on etiology, pathogenesis, clinical picture, diagnosis, differential diagnosis, neuroimaging, and pathomorphological assessment. After identifying all the articles that met the inclusion criteria and removing duplicate data, 35 literature sources on concurrent primary brain tumors and multiple sclerosis were selected. The conclusion on whether concurrent primary brain tumors and multiple sclerosis develop randomly or have common pathophysiological mechanisms is still under discussion. Potential causes of pathogenesis of both diseases include viral infection, chronic inflammation, neoplastic transformation, and involvement of neurotropic growth factors. The likelihood that two processes, demyelinating and neoplastic, can develop in parallel will never be underestimated. In such cases, strong clinical suspicion arises due to atypical clinical picture characterized by aggressive and rapidly growing neurological symptoms such as aphasia, spastic hemiparesis, epileptic seizures, or signs of intracranial hypertension. In MRI diagnosis, pathological findings such as single lesion of more than 2 cm; mass effect, edema, signal amplification in the form of ring-shaped shadow are the reasons for a more thorough examination and applying additional diagnostic methods: CT, MR spectroscopy, PET, CSF tests to determine oligoclonal antibodies and other markers content, cerebral biopsy. According to the literature, cases of concurrent primary brain tumors and multiple sclerosis are rare though described. Atypical clinical signs, neuroimaging data, and cerebral biopsy which is currently considered as the only method for making accurate diagnosis are helpful in the diagnostic process.

Clinical features and imaging analysis of primary bone lymphoma of the jaw

Objective: To investigate the clinical characteristics and imaging manifestations of primary bone lymphoma (PBL) located in the jaw. Methods: Clinical data of 14 PBL patients admitted to The First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019 were retrospectively analyzed, which including age, gender, location, chief complaint, laboratory test, imaging manifestations and so on. Results: Among the 14 PBL patients, 10 were male and 4 were female. Age range from 4 to 79 years, median age was 56 years old. There were 6 cases involved maxillary, 7 cases involved mandible and 1 case involved mandible and maxillary simultaneously. Twelve patients were admitted with local mass as the chief complaint, 3 had a history of toothache, 4 had loosen tooth and 2 had numbness of lips and cheeks. Two cases of oral mass with mucosal surface ulcer or abscess formation. One case complained of fever, night sweats and other systemic symptoms. The imaging findings showed 8 cases of osteolytic lesions, 1 case of sclerosis, 4 cases of mixed lesions and 1 case of cystic lesions. One case had periosteum reaction. In 12 cases, there was an obvious mass, which was characterized by the large soft-tissue mass and marrow changes were associated with surprisingly little cortical destruction. Conclusions: PBL is more common in middle aged male. The upper and lower jaw bones can be involved. Clinical and imaging manifestations lack characteristics, and common dental or periodontal symptoms such as toothache, tooth loosening, and paresthesia may occur. However, the imaging characteristics of large soft tissue masses with small degree of bone destruction can be used as an important basis for the differential diagnosis of osteomyelitis, squamous cell carcinoma, osteosarcoma and other diseases.

Is the primate-specific protein pLG72 affecting SOD1 functionality and superoxide formation?

pLG72 is a primate-specific protein of enigmatic function that was proposed to modulate mitochondria fragmentation and the activity of the peroxisomal enzyme D-amino acid oxidase (DAAO). DAAO is deputed to degradation of the NMDA receptor co-agonist D-serine in human brain and the R199W substitution in DAAO was identified in a familial case of amyotrophic lateral sclerosis (ALS). A recent work reported that U87 glioblastoma cells ectopically expressing pLG72 showed a lower proliferation, produced superoxide radicals, induced SOD1 aggregation and decreased its activity. Because of the role of SOD1 in eliminating ROS species and its relevance in ALS we evaluated the link between pLG72 and SOD1 using both wild-type pLG72 and its R30K variant related to schizophrenia susceptibility. In vitro studies on recombinant proteins excluded the establishment of a stable complex and that pLG72 could affect SOD1 activity and stability. At cellular level, ectopic expression of pLG72 in glioblastoma U87 cells did not affect cell viability and ROS/superoxide production: only caspase activity (a marker of apoptosis) was slightly increased in cells expressing the R30K pLG72 variant. SOD1 and pLG72 did not colocalize in transfected U87 glioblastoma cells: pLG72 largely localised to mitochondria and SOD1 was largely cytosolic. Moreover, the ectopic expression of pLG72 appeared not to alter the expression of SOD1 and its aggregation. Altogether, the combination of biochemical and cellular studies allow to exclude that pLG72 modulates SOD1 function and aggregation, thus that it could play a role in ALS susceptibility.

A case of encapsulating peritoneal sclerosis induced by peritoneal dialysis

A case of encapsulating peritoneal sclerosis induced by peritoneal dialysis

TO ASSESS SUBCLINICAL RNFL THICKNESS LOSS IN THE FELLOW EYES OF PATIENTS OF DEMYELINATING DISEASES.

An was Observational clinical study conducted on 30 patients who attended the OPD of upgraded department of Ophthalmology, Index Medical College Hospital & Research Centre, Indore. 60 eyes of 30 different patients of diagnosed cases of multiple sclerosis, neuromyelitis optica, and clinically isolated syndrome who had an H/O attack of Optic neuritis.
 Result: The difference between overall RNFL thickness in affected eyes and Fellow eyes is statistically significant. Chi square value is - 14.16.P value- 0.006 (<0.05)
 Severity of RNFL thickness loss in affected eyes of NMO (45.5µm; 83.34%) is more than MS (66.15µm; 65%). In CIS, RNFL thickness is highest (111.5µm)
 Conclusion: Severity of RNFL thickness loss is associated with the severity of visual impairment. Hence, can predict the progression of visual impairment in demyelinating diseases. Hence, evaluating the axonal damage, severity of visual impairment by measuring RNFL thickness loss is extremely useful in assessing the progression of visual loss and progression of demyelinating diseases. 
 Keywords: RNFL, Eyes, Demyelinating & Subclinical.

A Case of Systemic Sclerosis with ILD and Pulmonary Tuberculosis - A Rare Case Report

A Case of Systemic Sclerosis with ILD and Pulmonary Tuberculosis - A Rare Case Report