Diagnosis Of Sclerosis Research Articles

New Approaches to the Diagnosis, Clinical Course, and Goals of Therapy in Multiple Sclerosis and Related Disorders

The diagnosis, categorization, and treatment of multiple sclerosis (MS) and other demyelinating diseases have shifted over the past decade, and many of the fundamental principles of MS pathogenesis and clinical course are being rewritten. Fundamental issues include selecting the right disease-modifying therapy for someone with active disease and how, or even if, patients with purely progressive MS should be treated. This article provides an overview and introduction to the current thinking in MS diagnosis and therapy with an emphasis on the data-driven and proactive approach that has come to define the current state of the art.

What's in the Literature?

One of the first questions asked by patients and family members when a diagnosis of amyotrophic lateral sclerosis is made is "what about stem cells?" The term "stem cells" has attractiveness to it, with the assumption that stem cell treatment (stem nerve cells) can replace lost nerve cells. There are perhaps 2 types of stem cell trials, those that are vetted by the Food and Drug Administration and those that have no official oversight and whose results are infrequently published. The issue of the latter was discussed in the last edition of this column. The results of one of the formal stem cell trials now in the United States have been reported. Spinal muscular atrophy is a form of motor neuron disease affecting children and has a genetic cause, which has led to a feasibility study giving antisense oligonucleotides, and the results have also been reported. Biomarkers of amyotrophic lateral sclerosis are being sought, and the presence of neurofilaments is promising. Inflammatory neuropathies are an important group because they are treatable. Intravenous immune globulin is a commonly used agent, but a number of questions persist: one is efficacy among brands, another is the probability of a response, and a third is optimum dosing and taper schedules. A number of recent articles address these issues. The predictive value of single-fiber electromyography in determining which patients with ocular myasthenia will develop generalized disease, the risk of crisis after thymectomy, and 2 papers discussing new forms of congenital myasthenic syndrome are discussed. The risk of brain tumors, quality of life, and the assessment of trunk muscle strength in patients with type 1 myotonic dystrophy is reviewed. An article describing the discovery of mutations in SCN4A as a cause of congenital myopathy is discussed, as is one describing the occurrence of rhabdomyolysis in a group of patients subsequently discovered to have various forms of muscular dystrophy. Finally, articles describing the features of patients with inflammatory myopathies and Jo-1 and either 3-hydroxy-3-methylglutaryl-conezymea reductase or to signal recognition particle antibodies are reviewed.

Molecular Approach to Targeted Therapy for Multiple Sclerosis

The development and evolution of targeted therapy to any disease require the identification of targets amenable to treatment of patients. Here the pathogenetic signalling systems involved in multiple sclerosis are scrutinised to locate nodes of deregulation and dysfunction in order to devise strategies of drug development for targeted intervention. Oliogoclonal bands (OCB) are isoelectric focusing profiles of immunoglobulins synthesised in the central nervous system. OCBs enable the diagnosis of multiple sclerosis with high sensitivity and specificity and are related to the course of the disease and progression. The OCB patterns can be linked with the expression of angiogenic molecular species. Angiogenic signalling which has also been implicated in demyelination provides the option of using angiogenesis inhibitors in disease control. The PI3K (phosphoinositide 3-kinase)/Akt axis has emerged with a key role in myelination with its demonstrable links with mTOR mediated transcription of downstream target genes. Inflammatory signals and innate and acquired immunity from the activation of NF-κB (nuclear factor κB) responsive genes are considered. NF-κB signalling could be implicated in myelination. The transcription factor STAT (signal transducers and activators of transcription) and the EBV (Epstein- Barr virus) transcription factor BZLF1 contributing significantly to the disease process are a major environmental factor linked to MS. EBV can activate TGF (transforming growth factor) and VEGF (vascular endothelial growth factor) signalling. EBV microRNAs are reviewed as signalling mediators of pathogenesis. Stem cell transplantation therapy has lately gained much credence, so the current status of mesenchymal and hematopoietic stem cell therapy is reviewed with emphasis on the differential expression immune-related genes and operation of signalling systems.

Evaluation of the application of the European guidelines for diagnosis and clinical care of amyotrophic lateral sclerosis

Evaluation of the application of the European guidelines for diagnosis and clinical care of amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis: The Current World Situation

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown cause that affects mainly the motor neurons of the spinal cord, brain stem and brain. The pathogenesis is still obscure and the diagnosis is based on patient history and clinical examination. A handful of factors have been proposed to be associated with ALS;however, the only established risk factors to date are older age, male sex, and a family history of ALS. The familial cases have their historical importance in causative gene identifiation since through these discoveries much has been uncovered about ALS pathogenesis. The understanding of clinical and epidemiological factors associated with functional impairment is of fundamental for early adoption of measures to promote a better survival and a better quality of life. Rapid diagnosis of amyotrophic lateral sclerosis (ALS) and other neurological disorders is vital if future treatments are to be applied at an early disease stage. The current pace of discovery and identifiation of novel disease mechanisms in ALS is unprecedented. Advances in this area, however, have also introduced challenges in the heterogeneity of diagnostic defiitions affecting this patient population.

Reporting microvascular changes in nail fold capillaroscopy: A narrative review

Nailfold capillaroscopy (NFC) is a useful and noninvasive procedure for evaluating patients with signs and symptoms of microvascular disturbances such as Raynaud‟s phenomenon, either primary or secondary, with the ability to differentiate between the two. It is widely used for the diagnosis of systemic sclerosis (SSc), and the quantitative nature of the NFC report allows the monitoring of vascular changes in these patients and predicts their prognosis during follow-up visits. Five types of abnormal findings are reported with nailfold capillaroscopy (NFC), each having a specific definition and significance. The main goal of this article is to give a comprehensive review of the most widely accepted method of performing and reporting this procedure.

From Respiratory Distress to Diagnosis of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, which results in weakness and atrophy of voluntary skeletal muscles. ALS is the most common form of motor neuron disease (MND). It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS. The disease usually does not affect cognitive abilities, but causes muscle weakness. Respiratory function in the early stages of the disease is generally normal, shortness of breath occurs as the disease progresses. This paper has been submitted about ALS patient who was diagnosed and treated in intensive care unit followed by severe respiratory failure.

Analysis of hippocampus in multiple sclerosis-associated depression using image processing

Detecting brain structural changes from magnetic resonance (MR) images can facilitate early diagnosis and treatment of Multiple Sclerosis (MS), a neurodegenerative disease of central nervous system. We develop a novel volume and shape of hippocampus-based feature with Support Vector Machine (SVM) to detect brain structural changes as potential biomarkers. This approach requires pre-processing which is influenced by artefacts such as image distortion. We represent hippocampus segmentation based on watershed bottom hat filtering algorithm and morphological operations. The extracted features are used as criteria to categorise image features into two classes, i.e. healthy and patient. Only healthy and patient features are used to predict the disease status of new brain images. The results proved that the proposed architecture has high contribute to computer-aided diagnosis of MS. Our empirical evaluation has a superior retrieval and diagnosis performance when compared to the performance of other works.

New Diagnostic Criteria for Infantile Nystagmus. An Upgraded Nystagmus Clinical Approach

Purpose: CEMAS group has classified nystagmus comprehensively in 2001. From that time, attempts to make the subject as uniform as possible, needed continuous upgrading. This manuscript is an upgraded clinical approach for diagnosis of Irreversible Congenital Nystagmus, which is in addition to its being one of the major clinical features of intrinsic ocular diseases, is also a sign of inborn errors of myelination. Design: We will accompany the way to the diagnosis of congenital irreversible nystagmus of non-intrinsic eye disease origin, by highlighting all the symptoms and signs, which lead us to ascertain the exact etiologies, despite the important past classifications of nystagmus. Methods: We reviewed the appropriate relevant medical literature and looked for all the diseases, syndromes and triads in which the congenital nystagmus is one of their main components. We brought here in addition, a case report of an infant suffering from nystagmus for further refreshment. Results: In addition to its being a feature of several pediatric ophthalmic syndromes, congenital irreversible nystagmus (ICN) is also one of the exclusively important features in several nonophthalmic diseases, but not necessarily the first to appear. It is a main component for the diagnosis of Multiple Sclerosis, as well as other Leukodystrophies diagnosis, and to a lesser frequency in other syndromes. Conclusions: We recommend for Ophthalmologists to use the policy of “wait and see”, in infants complaining of irreversible nystagmus, which is not caused by local ophthalmic diseases. The appearance of characteristics, such as deafness, axial hypotonia, tremor and staccato speech and so on, in parallel with hyperreflexia, is the core of our upgraded flow chart of nystagmus clinical approach.

Contralateral recurrence of tumefactive demyelination

Tumefactive demyelination refers to large focal demyelinating lesions in the brain, which can be mistaken for malignancy. In some patients, these lesions are monophasic with a self-limited course; however, other patients demonstrate recurrent disease with new tumefactive or non-tumefactive lesions, and a subsequent diagnosis of relapsing-remitting multiple sclerosis is not uncommon. Owing to the limited data available in the literature, many questions about the patterns and prognostic significance of recurrent tumefactive lesions remain unanswered. The current case report involves a patient who recovered from tumefactive demyelination and presented two years later with a new recurrent tumefactive lesion in the contralateral brain.

Amyotrophic lateral sclerosis: What nurses need to know.

A MOTHER OF THREE teenage children, Mrs. S, 49, presented to her healthcare provider with bilateral leg twitching and weakness, difficulty swallowing, and fatigue that's worsened over the past few weeks. While she was on her daily morning walk, she tripped and fell. She experienced a small laceration to her leg, prompting her visit to the healthcare facility. Her husband said that she'd had periods of slurred speech over the past few months as well. She was alert and oriented, and her vital signs were all within normal limits.After an exam, her healthcare provider referred her to a neurologist who ordered magnetic resonance imaging (MRI), an electromyogram, and a full bloodwork panel. After multiple visits to rule out other causes, Mrs. S received the devastating diagnosis of amyotrophic lateral sclerosis (ALS).

BRAINSTEM AUDITORY EVOKED POTENTIALS FINDINGS IN ANKYLOSING SPONDYLITIS

Background. Ankylosing spondylitis (AS) is a chronic inflammatory potentially debilitating disease predominantly affecting the axial skeleton. A few intermittently published studies and research have proved the existence of some not yet explained neurophysiologic abnormalities in patients with AS. Objectives. The aim of this study was to investigate the brainstem auditory evoked potentials and its relation with clinical findings, laboratory tests and pharmacological therapy used in patients with AS. Material and method. Thirty-nine patients with AS were included in the study. The control group was composed of 50 healthy subjects. BAEP were recorded for all subjects. Patients were assessed by clinical specific tests, inflammatory laboratory tests, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and type of pharmacological therapy. Results. The results have shown differences between the control group and the patients with AS in most of the wave latencies. Correlations Schober test, Ott index, chest expansion measurement and BASDAI were significant for some waves. CRP seems to be more valuable than ESR as a possible marker for neurologic subclinical involvement. Axial AS is more likely to be associated with BAEP abnormalities. There were also differences between the group with TNF alpha blockers therapy comparative with the group with other therapies. Conclusions. This study highlights some abnormalities of BAEP in patients with AS. Diagnosis of multiple sclerosis or demyelination due to administration of TNF alpha blockers should be excluded in medical practice. Collaboration between neurologists and rheumatologists should be considered in monitoring AS patients.

EPIDEMIOLOGY, PATHOGENESIS, SYMPTOMS AND DIFFERENTIAL DIAGNOSIS OF MULTIPLE SCLEROSIS AND NEUROMYELITIS OPTICA [according the materials of Joint ACTRIMS-ECTRIMS meeting, September, 2014, Boston (MSJ, 2014, v.20, № S1)

The review presents the data on increasing the incidence of multiple sclerosis (MS) and possible causes of the increase. Possible modifying and non-modifying risk factors of MS are reviewed. The article presents the new data concerning value of grey matter lesions in brain and spinal cord, brain atrophy and biomarkers that could help in MS diagnosis and prediction of treatment response. Recently introduced terms “radiologically isolated syndrome” and “cortical relapses” are discussed. The difficulties in differential diagnosis between MS and similar diseases as neuromyelitis optica are presented. The differences between aquaporin-4 positive and negative patients with neuromyelitis optica are presented.

От клинически изолированного синдрома к достоверной диагностике рассеянного склероза и его эффективной терапии у детей

В статье изложены результаты 30-летнего опыта ранней диагностики рассеянного склероза у детей с использованием магнитно-резонансной томографии, зрительных и когнитивных вызванных потенциалов, биохимических и иммунологических исследований крови и спинномозговой жидкости. Авторами описаны варианты дебюта этого труднокурабельного инвалидизирующего заболевания у детей. Приведены схемы терапии, включая пульс-терапию солу-медролом, плазмаферез и внутривенный иммуноглобулин, а также опыт применения иммуномодуляторов у детей.

Automated Segmentation of MS Lesions in MR Images Based on an Information Theoretic Clustering and Contrast Transformations

Magnetic Resonance Imaging (MRI) plays a significant role in the current characterization and diagnosis of multiple sclerosis (MS) in radiological imaging. However, early detection of MS lesions from MRI still remains a challenging problem. In the present work, an information theoretic approach to cluster the voxels in MS lesions for automatic segmentation of lesions of various sizes in multi-contrast (T1, T2, PD-weighted) MR images, is applied. For accurate detection of MS lesions of various sizes, the skull-stripped brain data are rescaled and histogram manipulated prior to mapping the multi-contrast data to pseudo-color images. For automated segmentation of multiple sclerosis (MS) lesions in multi-contrast MRI, the improved jump method (IJM) clustering method has been enhanced via edge suppression for improved segmentation of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF) and MS lesions if present. From this preliminary clustering, a pseudo-color to grayscale conversion is designed to equalize the intensities of the normal brain tissues, leaving the MS lesions as outliers. Binary discrete and 8-bit fuzzy labels are then assigned to segment the MS lesions throughout the full brain. For validation of the proposed method, three brains, with mild, moderate and severe hyperintense MS lesions labeled as ground truth, were selected. The MS lesions of mild, moderate and severe categories were detected with a sensitivity of 80%, and 96%, and 94%, and with the corresponding Dice similarity coefficient (DSC) of 0.5175, 0.8739, and 0.8266 respectively. The MS lesions can also be clearly visualized in a transparent pseudo-color computer rendered 3D brain.

Increased incidence of Sjogren’s syndrome in systemic sclerosis: A nationwide population study

In the past, there were no studies to evaluate the incidence of Sjogren’s syndrome and its relationship with sex and age in patients with systemic sclerosis. In this study, we enrolled 2217 patients with systemic sclerosis and 6485 controls from Taiwan’s Registry of Catastrophic Illness database and National Health Insurance Research Database. Every patient with systemic sclerosis was matched to at most three controls by sex, age, month, and year of first diagnosis of systemic sclerosis. Standardized incidence ratio (SIR) of Sjogren’s syndrome in patients with systemic sclerosis and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). Both male and female patients with systemic sclerosis had higher incidences of Sjogren’s syndrome (SIR: 7.59, 95% CI = 2.97–19.51; SIR: 7.59, 95% CI = 5.56–10.42, respectively). The incidence of Sjogren’s syndrome in patients with systemic sclerosis was still higher compared with control when stratified according to age. Age at diagnosis of Sjogren’s syndrome was earlier in patients with systemic sclerosis in both male and female groups (p = 0.018; p < 0.001, respectively). Systemic sclerosis was associated with Sjogren’s syndrome after adjusting for age, sex, and various autoimmune diseases (HR: 5.98, 95% CI = 4.79–7.47, p < 0.001). Common cytokines, overlapping antibodies, and similar risk alleles were all potential causes of increased incidence of Sjogren’s syndrome in systemic sclerosis.

PP08.16 – 2439: Long-term follow-up of children with demyelinating diseases: Risk factors for multiple sclerosis outcome

Objective Demyelinating diseases of the central nervous system (CNS) in childhood are often presented as a monophasic event. But 30–57% of children after the first attack have a confirmed diagnosis of multiple sclerosis (MS) subsequently. This study describes clinical and magnetic resonance imaging (MRI) characteristics of the initial demyelinating episode and evaluates the risk factors of following diagnosis of MS. Methods This was a retrospective study of the child cohort who had been diagnosed with the first presentation of demyelinating disease at the Child Neurological Departments in Ekaterinburg, Russian Federation, during 1999–2011. Clinical features, MRI data and long-term prognosis were revieweld. The diagnosis of MS was established according to the Poser's (1983) and McDonald's (2001, 2005) criteria. Fisher exact test and Mann-Whitney U-test were used to evaluate the association of specific parameters to MS outcome. Results Sixty-seven children aged 2–17 (11.7±3.6 years) with the first neurologic episode of demyelinating disease of the CNS were identified. Among the initial symptoms optic neuritis (n=31), cranial nerve dysfunction (n=19) and ataxia (n=13) were predominant. None of the children had encephalopathy. Mean follow-up duration was 6.2±0.4 years (0.5 to 12 years). Overall, 30 (44.8%) of children have been diagnosed with multiple sclerosis. A half of them met the MS diagnostic criteria after 6 month from the first episode. The older age at the initial event correlated with MS outcome (13.2±0.7 years vs. 10.5±0.6 years of non-MS patients, p Conclusion The age, ataxic and brainstem signs and the presence of typical T2-hyperintense lesions on brain and spinal MRIs at onset mainly determine the long-term prognosis of MS outcome.

7. Neurophysiology in diagnosis and prognosis of multiple sclerosis in age of magnetic resonance imaging

Objective The advent of magnetic resonance imaging techniques has greatly reduced the diagnostic value of neurophysiological tests in MS, particularly evoked potentials. In disease progression, most of MS patients accumulate inflammatory lesions, axonal damage, and progressive brain atrophy, along with an increasing degree of disability. More promising is the utilization of neurophysiological tests to quantify the severity of white matter involvement. Methods Evoked potentials (EP) have been still used in multiple sclerosis (MS) especially in its early diagnosis. Recently, multimodal EPs appears to be a prognostic factor for disease progression ( Schlaeger et al., 2012 , Invernizzi et al., 2011 , Schlaeger et al., 2012 ). Deeper insights about causal and functional relationships in plasticity of the motor system in patients with MS were gained by neurophysiological techniques, predominantly by transcranial magnetic stimulation. Results Visual evoked potential (VEP) are preferentially used in early diagnosis of MS for detection of subclinical optic neuritis. Somatosensory (SEP) and motor (MEP) evoked potentials reveal subclinical lesions in the CNS and could be a supplementary diagnostic tests for sensory and motor system disturbances. MEP abnormalities correlate with the degree of motor impairment and disability. A number of functional imaging studies have assessed patterns of brain activation during simple motor tasks in MS patients and their relationship with CNS damage and motor function. Conclusion Evoked potentials are functional neurophysiological methods highly sensitive in revealing ,,silent lesions“ especially at the beginning of MS. Multimodal evoked potentials have indisputable benefit of prognostic value to determine non-responders, ,,benign“ course of the disease and identification of patients with significant disease progression. A battery of neurophysiological tests could be useful in monitoring the disease progression in individual patient and as surrogate endpoints in clinical trials. Supported by Research Project of Charles University PRVOUK P34, Czech Republic.

A retrospective clinical analysis of 16 patients with scleroderma renal crisis

To analyze the clinical features, laboratory tests, treatments and outcome of patients with scleroderma renal crisis (SRC). We retrospectively reviewed the clinical and laboratory data of 16 patients with scleroderma renal crisis in Peking Union Medical College Hospital from May 2004 to May 2013. The treatment and outcome of SRC patients were also retrospectively analyzed. There were a total of 16 SRC patients including 5 male patients and 11 females. The median age at SRC onset was (49.9 ± 12.3) years. It usually took 3.2 years from the diagnosis of systemic sclerosis (SSc) to SRC attack. Ten SRC patients belonged to diffuse cutaneous systemic sclerosis (dcSSc), and 6 patients were limited cutaneous systemic sclerosis (lcSSc). Among SRC patients, 16/16 were negative of anti-centromere antibodies (ACAs). All these 16 patients had hypertension and renal insufficiency, including 8 dialysis dependent after the onset of SRC and 7 with thrombotic microangiopathy. There were 3 patients receiving renal biopsy. The pathological findings were mainly summarized as intimal thickening and stenosis of renal arterioles. Among 13 patients with long-term followed-up, 11 patients received angiotensin converting enzyme inhibitors (ACEI), 5 patients died, 2 patients were dialysis dependent. Only 1 patient stopped dialysis after the combination treatment of ACEI and endothelin receptor antagonist. Another 5 patients didn't need dialysis. SRC usually occurred at the early course of SSc. dcSSc was more frequent than lcSSc. ACAs were rarely found in SRC patients. The immediate and sufficient use of ACEIs was still the cornerstone of SRC treatment. Future studies are needed to evaluate the efficacy of endothelin receptor antagonist in the treatment of SRC.

MRI Directional Diffusivity Values of Cervical Cord White Matter: Multiple Sclerosis Patients Vs. Healthy Controls

Background: Early diagnosis of multiple sclerosis (MS) can lead to preventive treatment and a favorable prognosis. Cervical spinal cord matter that appears normal on conventional MR images may be detected as abnormal using advanced MRI techniques. Objective: To pinpoint values and cervical spine locations in Diffusion Tensor Imaging (DTI) which best differentiate relapsing-remitting MS from healthy cases. Methods: 10 relapsing-remitting MS and 8 healthy control patients underwent DTI of the cervical spine. DTI values were measured in anterior, lateral and posterior cord locations. Results: Differences in values per location show statistical significance among all areas of the cord in both Normal Appearing White Matter (NAWM) and control groups. We derived an ADC cut-off value of 0.8 mm2/sec and λ2 value of 0.8 mm2/sec for optimal differentiation between NAWM and control. Using these cut-off metrics, values above 0.8 for Receiver Operating Characteristics (ROC) (area under curve) may be considered ‘good’ tests for pathology. ROC analysis showed that the optimal differentiation between NAWM of MS patients versus healthy controls was seen in the anterior area of the cervical cord. Sensitivity and specificity for λ2 and ADC are 85.7 & 75.0 and 85.7 & 75.0 respectively. Conclusion: DTI can detect early changes in relapsing-remitting MS with the anterior area of the cervical spine being the most representative of disease processes. Diagnostic cut-off values should be considered.