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  1. Multiple Sclerosis

    MedlinePlus

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the ... attacks healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  2. Multiple Sclerosis

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Multiple Sclerosis Information Page Condensed from Multiple Sclerosis: Hope Through ... en Español Additional resources from MedlinePlus What is Multiple Sclerosis? An unpredictable disease of the central nervous system, ...

  3. [Tuberous sclerosis].

    PubMed

    Metsähonkala, Liisa; Valanne, Leena; Anttonen, Anna-Kaisa

    2013-01-01

    Tuberous sclerosis is a polymorphic, dominantly inherited syndrome caused by an inactivating mutation in a tumor suppressor gene. The disease involves benign tumors in several distinct organs such as the skin, kidneys, heart and central nervous system. The tumors interfere with organ function, but only some exhibit a significant tendency to grow. The clinical picture of tuberous sclerosis varies from nearly symptomless to a severe disease. Treatment of growing tumors associated with tuberous sclerosis is changing significantly, since their growth can be suppressed with rapamycin and its derivatives. PMID:24159711

  4. Multiple sclerosis - resources

    MedlinePlus

    Resources - multiple sclerosis ... The following organizations provide information on multiple sclerosis : Multiple Sclerosis Foundation -- www.msfocus.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/multiple_sclerosis National ...

  5. Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  6. [Systemic sclerosis].

    PubMed

    Schinke, Susanne; Riemekasten, Gabriela

    2016-04-01

    Systemic sclerosis is a challenging and heterogeneous disease due to the involvement of multiple organs and the high impact on morbidity and quality of life. Lung fibrosis, pulmonary arterial hypertension, and cardiac manifestations are main causes of systemic sclerosis-related deaths. In addition, patients suffer from a various range of co-morbidities such as malnutrition, depression, osteoporosis, malignancies, which are increased in these patients and have to be identified and treated. Early assessment of organ damage is a key to therapeutic success. The discovery of pathogenic autoantibodies combined with increased evidence of effective immunosuppressive and vasoactive treatment strategies are major developments in the therapy of the disease. At present, several clinical studies are ongoing and some of the biological therapies are promising.

  7. Multiple Sclerosis

    PubMed Central

    2013-01-01

    Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. Much of what is known about MS has been learned from an animal model of the disease, experimental allergic encephalomyelitis. PMID:24381825

  8. Multiple Sclerosis.

    PubMed

    Schiess, Nicoline; Calabresi, Peter A

    2016-08-01

    It is estimated that there are 300,000 people with multiple sclerosis (MS) in the United States and 2.3 million worldwide. Each MS attack can affect function in cognitive, emotional, motoric, sensory, or visual domains. Patients are often struck in the prime of their lives as they attempt to move forward with career, and family. Since the previous 2010 Seminars in Neurology Pearls and Pitfalls issue, the world of MS has drastically changed and advanced. Here the authors address the ever-changing MS world in both treatment options and diagnostics, covering easily missed differential diagnoses, newly available immunomodulatory therapy, and the challenges of safely treating patients. PMID:27643903

  9. Fatigue and Multiple Sclerosis

    MedlinePlus

    Fatigue - National Multiple Sclerosis Society Skip to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area ... help* daily life for: positive-mom* The National MS Society is Here to Help Need More Information? ...

  10. National Multiple Sclerosis Society

    MedlinePlus

    ... Join the Community Stay Informed Corporate Support National Multiple Sclerosis Society Our Mission: People affected by MS can ... 10.5 Million in New Research to Stop Multiple Sclerosis, Restore Function and End MS Forever October 11, ...

  11. Multiple sclerosis

    PubMed Central

    Boster, Aaron L.; Racke, Michael K.

    2013-01-01

    Summary Preliminary studies have suggested that a high salt diet may play a role in the development of autoimmune disease and possibly multiple sclerosis (MS). Promising clinical trial results for 2 new therapies for MS have been reported. Dimethyl fumarate, also known by its investigational name BG-12, became the third oral disease-modifying therapy for MS to be Food and Drug Administration (FDA)–approved in March 2013. Interestingly, dimethyl fumarate served as the active compound used for the treatment of psoriasis for decades. Alemtuzumab remains under investigation and is not currently FDA-approved for treatment of MS. Other drugs currently approved for alternative indications are being investigated for use in MS. Additionally, an investigation of alternative dosing strategies for glatiramer acetate suggests that patients may benefit from a higher dose formulation and less frequent medication administration. Advances in basic science research have identified another potential autoantigenic target in MS, KIR4.1, which may provide further insight into MS pathophysiology. PMID:24175156

  12. Multiple sclerosis.

    PubMed

    Filippi, Massimo; Preziosa, Paolo; Rocca, Maria A

    2016-01-01

    Due to its sensitivity to the different multiple sclerosis (MS)-related abnormalities, magnetic resonance imaging (MRI) has become an established tool to diagnose MS and to monitor its evolution. MRI has been included in the diagnostic workup of patients with clinically isolated syndromes suggestive of MS, and ad hoc criteria have been proposed and are regularly updated. In patients with definite MS, the ability of conventional MRI techniques to explain patients' clinical status and progression of disability is still suboptimal. Several advanced MRI-based technologies have been applied to estimate overall MS burden in the different phases of the disease. Their use has allowed the heterogeneity of MS pathology in focal lesions, normal-appearing white matter and gray matter to be graded in vivo. Recently, additional features of MS pathology, including macrophage infiltration and abnormal iron deposition, have become quantifiable. All of this, combined with functional imaging techniques, is improving our understanding of the mechanisms associated with MS evolution. In the near future, the use of ultrahigh-field systems is likely to provide additional insight into disease pathophysiology. However, the utility of advanced MRI techniques in clinical trial monitoring and in assessing individual patients' response to treatment still needs to be assessed. PMID:27432676

  13. Genetics Home Reference: multiple sclerosis

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions multiple sclerosis multiple sclerosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Multiple sclerosis is a condition characterized by areas of damage ( ...

  14. [Psychoneuroimmunology and multiple sclerosis].

    PubMed

    Mel'nikov, M V; Pashchenkov, M V; Boĭko, A N

    2015-01-01

    In this review, the authors discuss interactions between mental, nervous and immune systems in multiple sclerosis, an impact of psycho-emotional stress on disease development and progression as well as possible mechanisms of these interactions.

  15. Amyotrophic Lateral Sclerosis

    MedlinePlus

    Amyotrophic lateral sclerosis (ALS) is a nervous system disease that attacks nerve cells called neurons in your ... people with ALS die from respiratory failure. The disease usually strikes between age 40 and 60. More ...

  16. Systemic sclerosis: Recent insights.

    PubMed

    Elhai, Muriel; Avouac, Jérôme; Kahan, André; Allanore, Yannick

    2015-05-01

    Systemic sclerosis is an orphan connective tissue disease characterized by alterations of the microvasculature, disturbances of the immune system and massive deposition of collagen and other matrix substances in the skin and internal organs. A major achievement of the recent years has been the validation of new classification criteria, allowing earlier diagnosis and earlier treatment of systemic sclerosis, before irreversible fibrosis and organ damage appeared ("window of opportunity"). Raynaud's phenomenon is usually the first sign of the disease and is considered as the main sentinel sign for the identification of very early systemic sclerosis. Systemic sclerosis is clinically heterogeneous and disease course remains unpredictable. Its prognosis depends on cardiopulmonary involvement and recent studies aim to identify serum or genetic biomarkers predictive of severe organ involvement. Moreover, the prospective follow-up of large cohorts has provided and will offer critical material to identify strong prognostic factors. Whereas the outcomes of vascular manifestations of the disease has been recently improved due to targeted therapy, recent data have highlighted that mortality has not changed over the past 40 years. This reflects the absence of efficacy of current available drugs to counteract the fibrotic process. Nevertheless, several targeted immunity therapies, commonly with proven efficacy in other immune diseases, are about to be investigated in systemic sclerosis. Indeed, promising results in small and open studies have been reported. This article deals with recent insights into classification criteria, pathogenesis, organ involvements, outcome and current and possible future therapeutic options in systemic sclerosis.

  17. Conjugal amyotrophic lateral sclerosis

    PubMed Central

    Dewitt, John D.; Kwon, Julia; Burton, Rebecca

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a disease characterized by progressive degeneration of motor neurons in the motor cortex, brainstem, and spinal cord. The incidence of sporadic ALS is 1.5 to 2.7 in 100,000, and the prevalence is 5.2 to 6.0 in 100,000. Conjugal ALS is even rarer than sporadic ALS. We report a case of conjugal ALS encountered in our outpatient neurology clinic. PMID:22275781

  18. [Autoantibodies in systemic sclerosis].

    PubMed

    Żebryk, Paweł; Puszczewicz, Mariusz

    2015-05-22

    Systemic sclerosis (SSc) is a rare connective tissue disorder, which leads to progressive fibrosis of many organs. Its course is characterized by the presence of two classical autoantibodies: anti-topoisomerase I (ATA, Scl-70) and anti-centromere (ACA). In recent years, the presence of antibodies against a wider range of antigens was demonstrated, namely: RNA polymerase III, fibrillarin, NOR90, Th/To, PM-Scl-100, PM-Scl-75, Ku, PDGFR, but their clinical significance is relatively little known and until recently the methods of their assessment were available only in specialized laboratories. More and more reports in the literature indicate existence of links between the presence of selected autoantibodies with clinical correlations i.e. anti-RNA polymerase III with scleroderma renal crisis or anti-Ku and myositis, arthritis and joint contractures. The importance of autoantibodies in the diagnostic process was underlined by their inclusion into the new ACR/EULAR 2013 classification criteria for systemic sclerosis. This work reviews the current knowledge on the clinical significance of autoantibodies in systemic sclerosis.

  19. Symptomatic therapy in multiple sclerosis

    PubMed Central

    Frohman, Teresa C.; Castro, Wanda; Shah, Anjali; Courtney, Ardith; Ortstadt, Jeffrey; Davis, Scott L.; Logan, Diana; Abraham, Thomas; Abraham, Jaspreet; Remington, Gina; Treadaway, Katherine; Graves, Donna; Hart, John; Stuve, Olaf; Lemack, Gary; Greenberg, Benjamin; Frohman, Elliot M.

    2011-01-01

    Multiple sclerosis is the most common disabling neurological disease of young adults. The ability to impact the quality of life of patients with multiple sclerosis should not only incorporate therapies that are disease modifying, but should also include a course of action for the global multidisciplinary management focused on quality of life and functional capabilities. PMID:21694806

  20. Electroconvulsive Therapy in Multiple Sclerosis.

    PubMed

    Steen, Katie; Narang, Puneet; Lippmann, Steven

    2015-01-01

    We performed a literature search regarding the safety and efficacy of electroconvulsive therapy in patients with multiple sclerosis and comorbid psychiatric symptoms. Literature review was conducted via PubMed databases. Of the cases we reviewed, most subjects with multiple sclerosis reported significant psychiatric symptom relief, with only a handful reporting neurologic deterioration. There was some evidence that active white matter lesions may be predictive of neurologic deterioration when electroconvulsive therapy is used in patients with multiple sclerosis. A brief description of the pathophysiology and effects of depression in patients with multiple sclerosis is also provided. Although no clinical recommendations or meaningful conclusions can be drawn without further investigation, the literature suggests that electroconvulsive therapy for treatment of psychiatric illnesses in patients with multiple sclerosis is safe and efficacious.

  1. Multiple sclerosis and infections.

    PubMed

    Venkatesan, Arun

    2015-01-01

    The intersection between infections and multiple sclerosis (MS) is complex and bidirectional. Numerous infectious agents have been posited to play a role in the initiation of MS, while emerging evidence suggests a potential relationship between established MS and the gut microbiome. As both systemic and CNS infections are major complications of MS, the clinical manifestations and evolving epidemiology of these infections over the lifespan of the MS patient are examined in this review. Data from animal models and human studies are discussed. PMID:26611265

  2. [Future challenges in multiple sclerosis].

    PubMed

    Fernández, Óscar

    2014-12-01

    Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. PMID:25732950

  3. Autonomic dysfunction in multiple sclerosis.

    PubMed

    Racosta, Juan Manuel; Kimpinski, Kurt; Morrow, Sarah Anne; Kremenchutzky, Marcelo

    2015-12-01

    Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications.

  4. Lupoid sclerosis: evaluation and treatment.

    PubMed

    Kaplan, P E; Betts, H B

    1977-01-01

    The history, physical examination and laboratory data are presented of a patient with multiple sclerosis and systemic lupus erythematosus. The rehabilitation medicine evaluation and course of therapy are reviewed. Other published cases of similar patients are reviewed.

  5. [Current therapy of multiple sclerosis].

    PubMed

    Antonio García Merino, J

    2014-12-01

    Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. PMID:25732945

  6. Animal models of systemic sclerosis.

    PubMed

    Morin, Florence; Kavian, Niloufar; Batteux, Frederic

    2015-01-01

    Systemic sclerosis is a systemic connective tissue disorder characterized by the fibrosis of the skin and certain visceral organs, vasculopathy, and immunological abnormalities. Several genetic and inducible animal models of SSc have been developed and are available for research studies. The purpose of this review is to summarize the various animal models of systemic sclerosis and describe the various contributions of these models in terms of understanding the pathophysiology of the condition and searching for new therapeutic strategies for this incurable disease.

  7. Immunology of Multiple Sclerosis.

    PubMed

    Sospedra, Mireia; Martin, Roland

    2016-04-01

    Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the central nervous system (CNS). A complex genetic background with the HLA-DR15 haplotype as the main genetic risk factor and over 100 mostly immune-related minor risk alleles as well as several environmental factors contribute to the etiology of MS. With respect to pathomechanisms, autoimmune inflammation in early MS is primarily mediated by adaptive immune responses and involves autoreactive T cells, B cells, and antibodies, while the later, chronic stages of MS are characterized by a compartmentalized immune response in the CNS with activated microglia and macrophages. A host of immune cells and mediators can contribute to the autoimmune process, but CNS-related factors such as localization of lesions, vulnerability of oligodendrocytes, neurons/axons, and secondary metabolic changes all play a role in the heterogeneous expression of the disease, including different pathologic lesion patterns, neuroimaging findings, disease courses, and severity and response to treatment. PMID:27116718

  8. Aging and multiple sclerosis.

    PubMed

    Sanai, Shaik Ahmed; Saini, Vasu; Benedict, Ralph Hb; Zivadinov, Robert; Teter, Barbara E; Ramanathan, Murali; Weinstock-Guttman, Bianca

    2016-05-01

    The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease-modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach. PMID:26895718

  9. Aging and multiple sclerosis.

    PubMed

    Sanai, Shaik Ahmed; Saini, Vasu; Benedict, Ralph Hb; Zivadinov, Robert; Teter, Barbara E; Ramanathan, Murali; Weinstock-Guttman, Bianca

    2016-05-01

    The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease-modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach.

  10. Vaccines in Multiple Sclerosis.

    PubMed

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy. PMID:26922172

  11. Pain in systemic sclerosis.

    PubMed

    Stisi, S; Sarzi-Puttini, P; Benucci, M; Biasi, G; Bellissimo, S; Talotta, R; Atzeni, F

    2014-01-01

    Chronic pain is a healthcare problem that significantly affects the mental health, and the professional and private life of patients. It can complicate many disorders and represents a common symptom of rheumatologic diseases, but the data on its prevalence is still limited. Pain is a ubiquitous problem in systemic sclerosis (SSc). SSc-related pain has been studied on the basis of biomedical models and is considered a symptom caused by the disease activity or previous tissue damage. Effective pain management is a primary goal of the treatment strategy, although this symptom in SSc has not yet been investigated in detail. However, these patients do not all respond adequately to pharmacological pain therapies, therefore in these cases a multimodal approach needs to be adopted. PMID:24938196

  12. Vaccines in Multiple Sclerosis.

    PubMed

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  13. Therapeutics for multiple sclerosis symptoms.

    PubMed

    Ben-Zacharia, Aliza Bitton

    2011-01-01

    Symptoms management in multiple sclerosis is an integral part of its care. Accurate assessment and addressing the different symptoms provides increased quality of life among patients with multiple sclerosis. Multiple sclerosis symptoms may be identified as primary, secondary, or tertiary symptoms. Primary symptoms, such as weakness, sensory loss, and ataxia, are directly related to demyelination and axonal loss. Secondary symptoms, such as urinary tract infections as a result of urinary retention, are a result of the primary symptoms. Tertiary symptoms, such as reactive depression or social isolation, are a result of the social and psychological consequences of the disease. Common multiple sclerosis symptoms include fatigue and weakness; decreased balance, spasticity and gait problems; depression and cognitive issues; bladder, bowel, and sexual deficits; visual and sensory loss; and neuropathic pain. Less-common symptoms include dysarthria and dysphagia, vertigo, and tremors. Rare symptoms in multiple sclerosis include seizures, hearing loss, and paralysis. Symptom management includes nonpharmacological methods, such as rehabilitation and psychosocial support, and pharmacological methods, ie, medications and surgical procedures. The keys to symptom management are awareness, knowledge, and coordination of care. Symptoms have to be recognized and management needs to be individualized. Multiple sclerosis therapeutics include nonpharmacological strategies that consist of lifestyle modifications, rehabilitation, social support, counseling, and pharmacological agents or surgical procedures. The goal is vigilant management to improve quality of life and promote realistic expectations and hope.

  14. Accelerated Cure Project for Multiple Sclerosis

    MedlinePlus

    ... main content Accelerating research toward a cure for multiple sclerosis Home Contact Us Search form Search Connect Volunteer ... is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

  15. Genetics Home Reference: tuberous sclerosis complex

    MedlinePlus

    ... phenotype in tuberous sclerosis. J Med Genet. 2004 Mar;41(3):203-7. Citation on PubMed or ... sclerosis complex: a review. Semin Pediatr Neurol. 2006 Mar;13(1):27-36. Review. Citation on PubMed ...

  16. Optineurin and amyotrophic lateral sclerosis.

    PubMed

    Maruyama, Hirofumi; Kawakami, Hideshi

    2013-07-01

    Amyotrophic lateral sclerosis is a devastating disease, and thus it is important to identify the causative gene and resolve the mechanism of the disease. We identified optineurin as a causative gene for amyotrophic lateral sclerosis. We found three types of mutations: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Optineurin negatively regulates the tumor necrosis factor-α-induced activation of nuclear factor kappa B. Nonsense and missense mutations abolished this function. Mutations related to amyotrophic lateral sclerosis also negated the inhibition of interferon regulatory factor-3. The missense mutation showed a cyotoplasmic distribution different from that of the wild type. There are no specific clinical symptoms related to optineurin. However, severe brain atrophy was detected in patients with homozygous deletion. Neuropathologically, an E478G patient showed transactive response DNA-binding protein of 43 kDa-positive neuronal intracytoplasmic inclusions in the spinal and medullary motor neurons. Furthermore, Golgi fragmentation was identified in 73% of this patient's anterior horn cells. In addition, optineurin is colocalized with fused in sarcoma in the basophilic inclusions of amyotrophic lateral sclerosis with fused in sarcoma mutations, and in basophilic inclusion body disease. These findings strongly suggest that optineurin is involved in the pathogenesis of amyotrophic lateral sclerosis.

  17. Viruses and Multiple Sclerosis

    PubMed Central

    Owens, Gregory P.; Gilden, Don; Burgoon, Mark P.; Yu, Xiaoli; Bennett, Jeffrey L.

    2012-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler’s murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel. PMID:22130640

  18. Pediatric Multiple Sclerosis.

    PubMed

    Lee, Ji Y; Chitnis, Tanuja

    2016-04-01

    Pediatric multiple sclerosis (MS) is a chronic inflammatory neurologic disease that is challenging to diagnose and treat. Although there are many clinical parallels between pediatric-onset MS and adult-onset MS, there is also accumulating evidence of distinguishing clinical features that may, in part, arise from development-specific, neuroimmune processes governing MS pathogenesis in children. Here the authors describe the clinical features, diagnosis, and treatment of pediatric MS, with a particular focus on describing clinical features and highlighting new developments that promise a better understanding of pediatric MS pathogenesis. An important task that lies ahead for pediatric neurologists is better understanding the early gene-environment interaction that precipitates the first demyelinating event in pediatric MS. This area is of particular importance for understanding the MS etiology and the natural history of pediatric MS. Such understanding should in turn inform new developments in diagnostic tools, long-term therapies, and much-needed biomarkers. Such biomarkers are not only valuable for defining the disease onset, but also for monitoring both the treatment response and a disease evolution that spans multiple decades in children with MS. PMID:27116721

  19. Viruses and Multiple Sclerosis

    PubMed Central

    Virtanen, Jussi Oskari; Jacobson, Steve

    2016-01-01

    Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents. PMID:22583435

  20. Neuroimaging in multiple sclerosis.

    PubMed

    Zivadinov, Robert; Cox, Jennifer L

    2007-01-01

    Conventional magnetic resonance imaging (MRI) has routinely been used to improve the accuracy of multiple sclerosis (MS) diagnosis and prognosis. Metrics derived from conventional MRI are now routinely used to detect therapeutic effects and extend clinical observations. However, conventional MRI measures, such as the use of lesion volume and count of gadolinium-enhancing and T2 lesions, have insufficient sensitivity and specificity to reveal the true degree of pathological changes occurring in MS. They cannot distinguish between inflammation, edema, demyelination, Wallerian degeneration, and axonal loss. In addition, they do not show a reliable correlation with clinical measures of disability and do not provide a complete assessment of therapeutic outcomes. Recent neuropathologic studies of typical chronic MS brains reveal macroscopic demyelination in cortical and deep gray matter (GM) that cannot be detected by currently available MRI techniques. Therefore, there is a pressing need for the development of newer MRI techniques to detect these lesions. Newer metrics of MRI analysis, including T1-weighted hypointense lesions, central nervous system atrophy measures, magnetization transfer imaging, magnetic resonance spectroscopy, and diffusion tensor imaging, are able to capture a more global picture of the range of tissue alterations caused by inflammation and neurodegeneration. At this time, they provide the only proof--albeit indirect--that important occult pathology is occurring in the GM. However, evidence is increasing that these nonconventional MRI measures correlate better with both existing and developing neurological impairment and disability when compared to conventional metrics. PMID:17531854

  1. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  2. Progressive multiple sclerosis

    PubMed Central

    Ontaneda, Daniel; Fox, Robert J.

    2015-01-01

    Purpose to Review To highlight the pathological features and clinical aspects of progressive multiple sclerosis (PMS). To highlight results of clinical trial experience to date and review ongoing clinical trials and perspective new treatment options. Explain the challenges of clinical trial design in PMS. Recent Findings MS has been identified as a chronic immune mediated disease, and the progressive phase of the disease appears to have significant neurodegenerative mechanisms. The classification of the course of PMS has been re-organized into categories of active vs. inactive inflammatory disease and the presence vs. absence of gradual disease progression. This differentiation allows clearer conceptualization of PMS and possibly even more efficient recruitment of PMS subjects into clinical trials. Clinical trial experience to date in PMS has been negative with anti-inflammatory medications used in relapsing MS. Simvastatin was recently tested in a phase II trial and showed a 43% reduction on annualized atrophy progression in secondary progressive MS. Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod, and anti-B-cell therapy ocrelizumab. Several efforts for development of outcome measures in PMS are ongoing. Summary PMS represents a significant challenge, as the pathogenesis of the disease is not well understood, no validated outcome metrics have been established, and clinical trial experience to date has been disappointing. Advances in the understanding of the disease and lessons learned in previous clinical trials are paving the way for successful development of disease modifying agents for this disease. PMID:25887766

  3. Pharmacotherapy of Systemic Sclerosis

    PubMed Central

    Postlethwaite, Arnold E.; Harris, L. Jeff; Raza, Syed H.; Kodura, Swapna; Akhigbe, Titilola

    2010-01-01

    Importance of the field Systemic-sclerosis (SSc) is an uncommon autoimmune disease with variable degrees of fibroproliferation in blood vessels and certain organs of the body. Presently, there is no cure for SSc. The purpose of this article is to review the current literature regarding pathogenesis and treatment of complications of SSc. Areas covered in this review All available articles regarding research related to SSc pathogenesis and treatment listed in the PubMed.gov database were searched, relevant articles were then reviewed and used as sources of information for this review. What the reader will gain This review attempts for the reader to highlight some current thought regarding mechanisms of SSc pathogenesis and how autoimmunity relates to vascular changes and fibrogenesis of the disease plus provide a review of results of completed clinical trials and current on-going clinical trials that address organ specific or global therapies for this disease which can aid physicians who provide medical care for patients with SSc. Take home message SSc is a complex autoimmune disease, the pathogenesis of which although not completely understood is under active study, and new insights into pathogenesis are continuously being discovered. Although there is no effective disease modifying treatment for patients with SSc, quality of life, morbidity and mortality can be improved by using targeted therapy directed at affecting the consequences of damage to lungs, blood vessels, kidneys and the gastrointestinal tract. Innovative approaches to treating SSc are under intense investigation. PMID:20210685

  4. Viruses and multiple sclerosis.

    PubMed

    Owens, Gregory P; Gilden, Don; Burgoon, Mark P; Yu, Xiaoli; Bennett, Jeffrey L

    2011-12-01

    Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler's murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel. PMID:22130640

  5. Albumin and multiple sclerosis.

    PubMed

    LeVine, Steven M

    2016-01-01

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth. PMID:27067000

  6. [Current description of multiple sclerosis].

    PubMed

    Río, Jordi; Montalbán, Xavier

    2014-12-01

    Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. PMID:25732942

  7. The Pathogenesis of Systemic Sclerosis.

    PubMed

    Stern, Edward P; Denton, Christopher P

    2015-08-01

    Systemic sclerosis is a multisystem disorder with a high associated mortality. The hallmark abnormalities of the disease are in the immune system, vasculature, and connective tissue. Systemic sclerosis occurs in susceptible individuals and is stimulated by initiating events that are poorly understood at present. In order for the disease phenotype to appear there is dysfunction in the homoeostatic mechanisms of immune tolerance, endothelial physiology, and extracellular matrix turnover. The progression of disease is not sequential but requires simultaneous dysfunction in these normal regulatory mechanisms. Better understanding of the interplay of these factors is likely to contribute to improved treatment options.

  8. [Current description of multiple sclerosis].

    PubMed

    Río, Jordi; Montalbán, Xavier

    2014-12-01

    Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications.

  9. Injectable Multiple Sclerosis Medications

    PubMed Central

    Tran, Zung Vu

    2012-01-01

    Although injection-site reactions (ISRs) occur with US Food and Drug Administration–approved injectable disease-modifying therapies (DMTs) for multiple sclerosis, there are currently few reports of real-world data on ISR management strategies or possible correlations between ISRs and patient demographics, disease characteristics, and missed injections. Patient-reported data on the use of DMTs, patient demographic and disease characteristics, missed injections, and ISR reduction strategies were collected via e-mail, a patient registry (www.ms-cam.org), and a Web-based survey. Of the 1380 respondents, 1201 (87%) indicated that they had used injectable DMTs, of whom 377 (31%) had used intramuscular (IM) interferon beta-1a (IFNβ-1a), 172 (14%) had used subcutaneous (SC) IFNβ-1a, 183 (15%) had used SC IFNβ-1b, and 469 (39%) had used glatiramer acetate (GA). The majority of respondents were older (73% were ≥40 years), female (79%), married or living with a partner (72%), white (94%), and nonsmoking (82%). Injection-site reaction incidence, grouped according to severity, varied among DMTs, with IM IFNβ-1a causing significantly (P < .001) fewer mild, moderate, or severe ISRs than the other therapies. Female sex and younger age were significantly (P < .05) associated with more moderate ISRs among users of IM IFNβ-1a, SC IFNβ-1b, and GA. Nonwhites reported severe ISRs more often than whites. For all DMTs injection-site massage and avoidance of sensitive sites were the most frequently used strategies to minimize ISRs. These data may help identify patients with characteristics associated with a higher risk for ISRs, allowing health-care professionals to provide anticipatory guidance to patients at risk for decreased adherence or discontinuation. PMID:24453732

  10. Zinc in Multiple Sclerosis

    PubMed Central

    Frederiksen, Jette Lautrup

    2016-01-01

    In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS. Searching the databases PubMed and EMBASE as well as going through reference lists in included articles 24 studies were found measuring Zn in patients with MS. Of these, 13 met inclusion criteria and were included in the meta-analysis. The result of the meta-analysis shows a reduction in serum or plasma Zn levels in patients with MS with a 95% CI of [−3.66, −0.93] and a p value of .001 for the difference in Zn concentration in μM. One of six studies measuring cerebrospinal fluid, Zn levels found a significant increase in patients with MS with controls. The studies measuring whole blood and erythrocyte Zn levels found up to several times higher levels of Zn in patients with MS compared with healthy controls with decreasing levels during attacks in relapsing-remitting MS patients. Future studies measuring serum or plasma Zn are encouraged to analyze their data through homogenous MS patient subgroups on especially age, sex, and disease subtype since the difference in serum or plasma Zn in these subgroups have been found to be significantly different. It is hypothesized that local alterations of Zn may be actively involved in the pathogenesis of MS. PMID:27282383

  11. Amyotrophic lateral sclerosis mimic syndromes

    PubMed Central

    Ghasemi, Majid

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) misdiagnosis has many broad implications for the patient and the neurologist. Potentially curative treatments exist for certain ALS mimic syndromes, but delay in starting these therapies may have an unfavorable effect on outcome. Hence, it is important to exclude similar conditions. In this review, we discuss some of the important mimics of ALS. PMID:27326363

  12. Hippocampal Sclerosis: Causes and Prevention.

    PubMed

    Walker, Matthew Charles

    2015-06-01

    Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures. PMID:26060898

  13. Childhood Multiple Sclerosis: A Review

    ERIC Educational Resources Information Center

    Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan

    2006-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when…

  14. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  15. Defining secondary progressive multiple sclerosis.

    PubMed

    Lorscheider, Johannes; Buzzard, Katherine; Jokubaitis, Vilija; Spelman, Tim; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, François; Grammond, Pierre; Hupperts, Raymond; Alroughani, Raed; Sola, Patrizia; Boz, Cavit; Pucci, Eugenio; Lechner-Scott, Jeanette; Bergamaschi, Roberto; Oreja-Guevara, Celia; Iuliano, Gerardo; Van Pesch, Vincent; Granella, Franco; Ramo-Tello, Cristina; Spitaleri, Daniele; Petersen, Thor; Slee, Mark; Verheul, Freek; Ampapa, Radek; Amato, Maria Pia; McCombe, Pamela; Vucic, Steve; Sánchez Menoyo, José Luis; Cristiano, Edgardo; Barnett, Michael H; Hodgkinson, Suzanne; Olascoaga, Javier; Saladino, Maria Laura; Gray, Orla; Shaw, Cameron; Moore, Fraser; Butzkueven, Helmut; Kalincik, Tomas

    2016-09-01

    A number of studies have been conducted with the onset of secondary progressive multiple sclerosis as an inclusion criterion or an outcome of interest. However, a standardized objective definition of secondary progressive multiple sclerosis has been lacking. The aim of this work was to evaluate the accuracy and feasibility of an objective definition for secondary progressive multiple sclerosis, to enable comparability of future research studies. Using MSBase, a large, prospectively acquired, global cohort study, we analysed the accuracy of 576 data-derived onset definitions for secondary progressive multiple sclerosis and first compared these to a consensus opinion of three neurologists. All definitions were then evaluated against 5-year disease outcomes post-assignment of secondary progressive multiple sclerosis: sustained disability, subsequent sustained progression, positive disability trajectory, and accumulation of severe disability. The five best performing definitions were further investigated for their timeliness and overall disability burden. A total of 17 356 patients were analysed. The best definition included a 3-strata progression magnitude in the absence of a relapse, confirmed after 3 months within the leading Functional System and required an Expanded Disability Status Scale step ≥4 and pyramidal score ≥2. It reached an accuracy of 87% compared to the consensus diagnosis. Seventy-eight per cent of the identified patients showed a positive disability trajectory and 70% reached significant disability after 5 years. The time until half of all patients were diagnosed was 32.6 years (95% confidence interval 32-33.6) after disease onset compared with the physicians' diagnosis at 36 (35-39) years. The identified patients experienced a greater disease burden [median annualized area under the disability-time curve 4.7 (quartiles 3.6, 6.0)] versus non-progressive patients [1.8 (1.2, 1.9)]. This objective definition of secondary progressive multiple

  16. Epidemiology of multiple sclerosis.

    PubMed

    Leray, E; Moreau, T; Fromont, A; Edan, G

    2016-01-01

    Multiple sclerosis (MS) is the most frequently seen demyelinating disease, with a prevalence that varies considerably, from high levels in North America and Europe (>100/100,000 inhabitants) to low rates in Eastern Asia and sub-Saharan Africa (2/100,000 population). Knowledge of the geographical distribution of the disease and its survival data, and a better understanding of the natural history of the disease, have improved our understanding of the respective roles of endogenous and exogenous causes of MS. Concerning mortality, in a large French cohort of 27,603 patients, there was no difference between MS patients and controls in the first 20 years of the disease, although life expectancy was reduced by 6-7 years in MS patients. In 2004, the prevalence of MS in France was 94.7/100,000 population, according to data from the French National Health Insurance Agency for Salaried Workers (Caisse nationale d'assurance maladie des travailleurs Salariés [CNAM-TS]), which insures 87% of the French population. This prevalence was higher in the North and East of France. In several countries, including France, the gender ratio for MS incidence (women/men) went from 2/1 to 3/1 from the 1950s to the 2000s, but only for the relapsing-remitting form. As for risk factors of MS, the most pertinent environmental factors are infection with Epstein-Barr virus (EBV), especially if it arises after childhood and is symptomatic. The role of smoking in MS risk has been confirmed, but is modest. In contrast, vaccines, stress, traumatic events and allergies have not been identified as risk factors, while the involvement of vitamin D has yet to be confirmed. From a genetic point of view, the association between HLA-DRB1*15:01 and a high risk of MS has been known for decades. More recently, immunogenetic markers have been identified (IL2RA, IL7RA) and, in particular thanks to studies of genome-wide associations, more than 100 genetic variants have been reported. Most of these are involved in

  17. Multiple sclerosis - New treatment modalities

    PubMed Central

    Totaro, Rocco; Di Carmine, Caterina; Marini, Carmine; Carolei, Antonio

    2015-01-01

    Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference. PMID:26831413

  18. Olfactory loss in multiple sclerosis.

    PubMed

    Zivadinov, R; Zorzon, M; Monti Bragadin, L; Pagliaro, G; Cazzato, G

    1999-10-15

    The objectives of the present study were to test odor identification ability in patients with multiple sclerosis (MS) and to examine possible correlations between smell identification test scores and various clinical variables. We performed a case-control study comparing the Cross Cultural Smell Identification Test scores of 40 patients with definite multiple sclerosis with those obtained in 40 age-, sex- and smoking-habit-matched healthy controls. The neurological impairment, the disability, the cognitive performances and the psychological functioning were also assessed. Patients with multiple sclerosis scored significantly poorer than controls on the Cross-Cultural Smell Identification Test (P<0.001). Olfactory function was borderline normal in four (10%) and abnormal in five (12.5%) MS patients, whereas it was normal in all controls (P<0.02). Significant correlations between the smell identification score and symptoms of anxiety (r=-0.43, P=0.006), depression (r=-0.42, P=0. 008) and severity of neurological impairment (r=-0.32, P=0.05) were found. Only two (5%) patients with multiple sclerosis reported having episodes of smell loss, suggesting a low level of awareness of this problem. Although smell changes are rarely reported, olfactory function is impaired in a considerable number of patients with MS. The observed association between decreased odor identification ability and symptoms of anxiety and depression in our patients suggests that mood and anxiety disorders have to be considered in assessing olfaction in MS patients. Clearly, smell disturbances deserve greater attention from health professionals and caregivers dealing with such patients.

  19. [Special cases of multiple sclerosis].

    PubMed

    Mendibe Bilbao, Mar

    2014-12-01

    Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions. PMID:25732948

  20. [Special cases of multiple sclerosis].

    PubMed

    Mendibe Bilbao, Mar

    2014-12-01

    Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions.

  1. Update on multiple sclerosis treatments.

    PubMed

    Bridel, Claire; Lalive, Patrice H

    2014-01-01

    Relapsing-remitting multiple sclerosis (RRMS) management has dramatically changed over the past decade. New drugs have arrived on the market, allowing for more individualised treatment selection. However, this diversity has increased the complexity of RRMS patient follow-up. In this review, we provide summarised information about treatment efficacy, potential side-effects, follow-up recommendations, vaccinations, and pregnancy safety issues for all currently available disease modifying therapies and those awaiting approval. PMID:25247669

  2. Coping with Multiple Sclerosis Scale

    PubMed Central

    Parkerson, Holly A.; Kehler, Melissa D.; Sharpe, Donald

    2016-01-01

    Background: The Coping with Multiple Sclerosis Scale (CMSS) was developed to assess coping strategies specific to multiple sclerosis (MS). Despite its wide application in MS research, psychometric support for the CMSS remains limited to the initial factor analytic investigation by Pakenham in 2001. Methods: The current investigation assessed the factor structure and construct validity of the CMSS. Participants with MS (N = 453) completed the CMSS, as well as measures of disability related to MS (Multiple Sclerosis Impact Scale), quality of life (World Health Organization Quality of Life Brief Scale), and anxiety and depression (Hospital Anxiety and Depression Scale). Results: The original factor structure reported by Pakenham was a poor fit to the data. An alternate seven-factor structure was identified using exploratory factor analysis. Although there were some similarities with the existing CMSS subscales, differences in factor content and item loadings were found. Relationships between the revised CMSS subscales and additional measures were assessed, and the findings were consistent with previous research. Conclusions: Refinement of the CMSS is suggested, especially for subscales related to acceptance and avoidance strategies. Until further research is conducted on the revised CMSS, it is recommended that the original CMSS continue to be administered. Clinicians and researchers should be mindful of lack of support for the acceptance and avoidance subscales and should seek additional scales to assess these areas. PMID:27551244

  3. Idiopathic segmental sclerosis of vertebral bodies

    SciTech Connect

    McCarthy, E.F.; Dorfman, H.D.

    1982-12-01

    Five cases of idiopathic vetebral sclerosis are presented. The features of this condition are segmental vertebral sclerosis of a single lumbar vertebra in a young adult without disc space narrowing or alteration of vertebral contour. The differential diagnosis is discussed. Lumbar vertebra biopsies of three patients showed reactive nonspecific osteosclerosis.

  4. Systemic Sclerosis: Commonly Asked Questions by Rheumatologists

    PubMed Central

    Young, Amber; Khanna, Dinesh

    2016-01-01

    Systemic sclerosis is a rare autoimmune disorder with significant morbidity and mortality due to multi-organ system involvement. Early diagnosis and screening for organ involvement is critical as earlier treatment appears to improve function and may impact mortality. The purpose of this article is to address some of the commonly asked questions by rheumatologists on systemic sclerosis. PMID:25807095

  5. Demyelination of subcortical nuclei in multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

    2016-02-01

    Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

  6. Patient-Reported Outcome Measures in Systemic Sclerosis (Scleroderma).

    PubMed

    Pellar, Russell E; Tingey, Theresa M; Pope, Janet Elizabeth

    2016-05-01

    Scleroderma (systemic sclerosis) is a rare autoimmune connective tissue disease that can damage multiple organs and reduce quality of life. Patient-reported outcome measures capture the patient's perspective. Some measures are specific to systemic sclerosis and others are general. Patient-reported outcomes in systemic sclerosis are important to aid in understanding the impact of systemic sclerosis on patients. PMID:27133491

  7. Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

    PubMed

    Pryce, Gareth; Baker, David

    2015-01-01

    There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS). These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms. This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS. PMID:26408162

  8. Endocannabinoids in Multiple Sclerosis and Amyotrophic Lateral Sclerosis.

    PubMed

    Pryce, Gareth; Baker, David

    2015-01-01

    There are numerous reports that people with multiple sclerosis (MS) have for many years been self-medicating with illegal street cannabis or more recently medicinal cannabis to alleviate the symptoms associated with MS and also amyotrophic lateral sclerosis (ALS). These anecdotal reports have been confirmed by data from animal models and more recently clinical trials on the ability of cannabinoids to alleviate limb spasticity, a common feature of progressive MS (and also ALS) and neurodegeneration. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have efficacy, not only in symptom relief but also as neuroprotective agents which may slow disease progression and thus delay the onset of symptoms. This review discusses what we now know about the endocannabinoid system as it relates to MS and ALS and also the therapeutic potential of cannabinoid therapeutics as disease-modifying or symptom control agents, as well as future therapeutic strategies including the potential for slowing disease progression in MS and ALS.

  9. Symptomatic management in multiple sclerosis

    PubMed Central

    Shah, Pushkar

    2015-01-01

    Multiple sclerosis (MS) is the commonest cause of disability in young adults. While there is increasing choice and better treatments available for delaying disease progression, there are still, very few, effective symptomatic treatments. For many patients such as those with primary progressive MS (PPMS) and those that inevitably become secondary progressive, symptom management is the only treatment available. MS related symptoms are complex, interrelated, and can be interdependent. It requires good understanding of the condition, a holistic multidisciplinary approach, and above all, patient education and empowerment. PMID:26538847

  10. Skin imaging in systemic sclerosis

    PubMed Central

    Kang, Taeyoung; Abignano, Giuseppina; Lettieri, Giovanni; Wakefield, Richard J.; Emery, Paul; Del Galdo, Francesco

    2014-01-01

    Fibrotic involvement of the skin is a cardinal feature of systemic sclerosis (SSc). The extent of skin involvement is associated with internal organ involvement, coinciding with more severe disease course and poor prognosis. A palpation-based semi-quantitative score, the modified Rodnan skin score, is widely used for the assessment of skin involvement, but it is entailed by significant limitations. More objective approaches to measure skin involvement employing imaging have been explored continuously in the past decades and are currently advancing. Here, we review the use of different imaging techniques for the assessment of skin involvement in patients with SSc, focusing mainly on ultrasound, magnetic resonance imaging, and optical coherence tomography.

  11. Evoked potentials in multiple sclerosis.

    PubMed

    Kraft, George H

    2013-11-01

    Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs.

  12. [Driving ability with multiple sclerosis].

    PubMed

    Küst, J; Dettmers, C

    2014-07-01

    Driving is an important issue for young patients, especially for those whose walking capacity is impaired. Driving might support the patient's social and vocational participation. The question as to whether a patient with multiple sclerosis (MS) is restricted in the ability to drive a car depends on neurological and neuropsychological deficits, self-awareness, insight into deficits and ability to compensate for loss of function. Because of the enormous variability of symptoms in MS the question is highly individualized. A practical driving test under supervision of a driving instructor (possibly accompanied by a neuropsychologist) might be helpful in providing both patient and relatives adequate feedback on driving abilities. PMID:24906536

  13. Neurotherapeutic Strategies for Multiple Sclerosis.

    PubMed

    Frohman, Teresa C; Beh, Shin C; Kildebeck, Eric J; Narayan, Ram; Treadaway, Katherine; Greenberg, Benjamin; Frohman, Elliot M

    2016-08-01

    Multiple sclerosis (MS) is the most common disabling neurologic disease of young adults. There are now 16 US Food and Drug Administration (FDA)-approved disease-modifying therapies for MS as well as a cohort of other agents commonly used in practice when conventional therapies prove inadequate. This article discusses approved FDA therapies as well as commonly used practice-based therapies for MS, as well as those therapies that can be used in patients attempting to become pregnant, or in patients with an established pregnancy, who require concomitant treatment secondary to recalcitrant disease activity. PMID:27445239

  14. Newer therapies for multiple sclerosis

    PubMed Central

    Coles, Alasdair

    2015-01-01

    The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years), the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an “escalation” or “induction” approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects. PMID:26538846

  15. Newer therapies for multiple sclerosis.

    PubMed

    Coles, Alasdair

    2015-09-01

    The newer immunotherapies for multiple sclerosis (fingolimod, natalizumab, dimethyl fumarate, teriflunomide, alemtuzumab) offer advantages of efficacy or tolerability over the injectable therapies of the 1990s. But they also have greater risks. As further treatments emerge (daclizumab and ocrelizumab are likely to be licensed in the next two years), the physician needs to be able to place them within a complex landscape of drugs and a specific treatment strategy, which may be an "escalation" or "induction" approach. Whilst on treatment, neurologist and patient need to be vigilant to signs of disease breakthrough or adverse effects. PMID:26538846

  16. Symptomatic fatigue in multiple sclerosis.

    PubMed

    Freal, J E; Kraft, G H; Coryell, J K

    1984-03-01

    Symptomatic fatigue has not been investigated previously in a multiple sclerosis population. Potential subjects were the 78% of 656 individuals with multiple sclerosis who indicated in a previous study that they experienced symptomatic fatigue. Three hundred nine subjects (60%) returned a follow-up questionnaire on symptomatic fatigue. Ninety percent described fatigue as "tiredness or the need to rest," but 43% of them indicated that "sleepiness" was part of the symptomatology. In 48% fatigue made other MS symptoms worse. Fatigue tended to occur in the late afternoon and evening. It occurred almost daily for more than 66% of the subjects. In 47% of the subjects fatigue usually subsided within a few hours; in other subjects occurrences were of variable length (40%) or lasted between 6 and 24 hours (8%). Ninety percent said that fatigue was worse at warmer environmental temperatures. Fatigue was worse for 83% after "vigorous exercise" and for 64% after "moderate exercise" although 15% reported that moderate exercise helped to reduce fatigue. Meditation, some drugs, and cooling with water reduced fatigue in a majority of the small proportion of the population trying these techniques. A planned daily schedule of activity and rest seemed to be a partially effective response to symptomatic fatigue for the majority of subjects studied.

  17. Cognitive impairment in multiple sclerosis.

    PubMed

    Jongen, P J; Ter Horst, A T; Brands, A M

    2012-04-01

    Cognitive impairment occurs in 40-65% of multiple sclerosis (MS) patients, typically involving complex attention, information processing speed, (episodic) memory and executive functions. It is seen in the subclinical radiologically isolated syndrome, clinically isolated syndrome, and all phases of clinical MS. In pediatric-onset MS cognition is frequently impaired and worsens relatively rapidly. Cognitive impairment often affects personal life and vocational status. Depression, anxiety and fatigue aggravate symptoms, whereas cognitive reserve partially protects. Cognitive dysfunction correlates to brain magnetic resonance imaging (MRI) lesion volumes and (regional) atrophy, and degree of and increase in MRI abnormalities predict further worsening. Experimental MRI indicates a crucial role for (focal) cortical lesions and atrophy, abnormal cortical integrity, and early changes in normal appearing brain tissue. Functional MRI suggests compensatory reorganization and adaptation changes in neural activities. Screening tools are the Brief Repeatable Neuropsychological Battery, Symbol Digit Modalities Test and Audio Recorded Cognitive Screen. The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MS) is used for formal neuropsychological evaluation. What constitutes a clinically relevant change and how to optimally monitor cognition are issues to be settled. In relapsing-remitting MS timely and adequate disease modifying drug treatment may stabilize or possibly improve cognition. There is no evidence-based symptomatic drug treatment, nor are there optimal non-pharmacological approaches. Leisure activities enhance cognitive reserve. Cognitive rehabilitation in MS patients is still in its infancy. Cognitive behavioral therapy, exercise, and education programs are promising psychosocial interventions to improve coping and lessen cognitive symptoms.

  18. Novel Insights and Therapeutics in Multiple Sclerosis.

    PubMed

    Wagner, Catriona A; Goverman, Joan M

    2015-01-01

    The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease.

  19. Novel Insights and Therapeutics in Multiple Sclerosis

    PubMed Central

    Wagner, Catriona A.; Goverman, Joan M.

    2015-01-01

    The last twelve years have witnessed the development of new therapies for relapsing-remitting multiple sclerosis that demonstrate increased efficacy relative to previous therapies. Many of these new drugs target the inflammatory phase of disease by manipulating different aspects of the immune system. While these new treatments are promising, the development of therapies for patients with progressive multiple sclerosis remains a significant challenge. We discuss the distinct mechanisms that may contribute to these two types of multiple sclerosis and the implications of these differences in the development of new therapeutic targets for this debilitating disease. PMID:26339480

  20. Association between polyneuritis and multiple sclerosis.

    PubMed Central

    Forrester, C; Lascelles, R G

    1979-01-01

    We report two cases in which multiple sclerosis and inflammatory polyneuritis occurred separately, and suggest that this association supports the idea that the two conditions may have an aetiological link. PMID:228012

  1. Genetics Home Reference: amyotrophic lateral sclerosis

    MedlinePlus

    ... amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum Mol Genet. 2014 Jul 1;23(13): ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

  2. Multiple sclerosis: Experimental and clinical aspects

    SciTech Connect

    Scheinberg, L.; Raine, C.S.

    1984-01-01

    This book discusses the experimental and clinical aspects of multiple sclerosis. Specifically discussed are - Association of Epstein Barr Virus with pathology of central nervous system; immunology of viruses; and immunosuppression.

  3. Epidemiology in multiple sclerosis: a pilgrim's progress.

    PubMed

    Kurtzke, John F

    2013-09-01

    There was more neurology taught under Harold G. Wolff at Cornell University Medical College in New York than perhaps anywhere else in the country when I attended from 1948 to 1952. I took my residency at the Veterans Administration Hospital in the Bronx, New York, a teaching hospital of Cornell, with Wolff as my Director of Training. While a resident, we thought we had found a treatment for multiple sclerosis. To test our conclusion, the first Class 1 treatment trial ever conducted for multiple sclerosis was performed. This showed no effect, but the participants began investigating multiple sclerosis among the 16 million persons at prime age for symptom onset who had served in the military in World War II. This led me to study its epidemiology worldwide, beginning with a detailed review of all published population-based estimates of frequency. Among these were nationwide surveys from Sweden, Denmark, Switzerland and later Norway and Finland, which showed in each country a concentration of the significantly high regions into contiguous areas forming a single 'focus' in each land, maximal in Denmark under the age of 15 years. The primary locus of high frequency multiple sclerosis seemed to be in the south-central inland lake region of Sweden, with spread to its contiguous neighbours. These concentrations in time and space indicated that multiple sclerosis was a disease probably acquired in early adolescence. Migration studies supported this: moves from high to low showed retention of birthplace risk only for those aged >15 years, whereas opposite moves indicated susceptibility limited to some 11-45 year olds. Epidemics of multiple sclerosis would suggest the disease is not only acquired but also infectious. If an infectious origin were true, transmission would have to occur before clinical onset, and would have to involve a much greater number of subjects than clinically involved. I believe there have been epidemics in Iceland, Shetland-Orkney and the Faroe Islands

  4. Class II HLA antigens in multiple sclerosis.

    PubMed Central

    Miller, D H; Hornabrook, R W; Dagger, J; Fong, R

    1989-01-01

    HLA typing in Wellington revealed a stronger association of multiple sclerosis with DR2 than with DQw1. The association with DQw1 appeared to be due to linkage disequilibrium of this antigen with DR2. These results, when considered in conjunction with other studies, are most easily explained by the hypothesis that susceptibility to multiple sclerosis is influenced by multiple risk factors, with DR2 being an important risk factor in Caucasoid populations. PMID:2732726

  5. Recency effect in multiple sclerosis.

    PubMed

    Godoy, J F; Perez, M; Sanchez-Barrera, M B; Muela, J A; Mari-Beffa, P; Puente, A

    1996-05-01

    The main object of this study was to test acquisition-retrieval deficits in multiple sclerosis (MS) patients A Spanish version of the Rey Auditory-Verbal Test (RAVLT) (Rey 1964) was used with an MS group (n=10 subjects) and a control group (n=10) Different measurements were obtained with the RAVLT memory span, a learning curve, and a curve of serial position of words The results revealed no differences between groups in memory span and learning curve, but significant differences were found in the curve of serial position No revency effect in the immediate form of theRAVLT was seen These results are discussed with reference to the work of Baddelaey and Hitch (1993) regarding recency effects and related literature on the acquisition-retrieval deficits in MS patients.

  6. Musculoskeletal involvement in systemic sclerosis.

    PubMed

    Randone, Silvia Bellando; Guiducci, Serena; Cerinic, Marco Matucci

    2008-04-01

    Musculoskeletal involvement is more frequent than expected in patients with systemic sclerosis (SSc) and is a major cause of disability, even if the prognosis of the disease largely depends on visceral involvement. The most common clinical feature of musculoskeletal involvement is arthralgia; less frequent features are arthritis, flexion contractures, stiffness (affecting predominantly fingers, wrists and ankles), proximal muscle weakness (mainly of the shoulder and hip) and tendon sheath involvement. Tendon friction rubs are predictive of poor prognosis. If musculoskeletal involvement is suspected, serum creatinine phosphokinase, aldolase, lactate dehydrogenase, alkaline phosphate, rheumatoid factor and anticyclic citrullinated peptide autoantibodies should be checked routinely. Treatment for muscle involvement has not yet been considered adequately and, in the future, it is to be hoped that clinical trials will identify new drugs to control this aspect of SSc, which seriously compromises patients' quality of life. PMID:18455689

  7. Erectile Dysfunction in Systemic Sclerosis.

    PubMed

    Jaeger, Veronika K; Walker, Ulrich A

    2016-08-01

    Erectile dysfunction (ED) is a major issue in systemic sclerosis (SSc) as it is observed in around 80 to 90 % of men with this connective tissue disease. ED greatly impacts the quality of life and should be actively addressed as a common complication. Whereas ED in the general population is usually associated with risk factors for atherosclerosis as well as cardiovascular disease, the main aetiology of ED in SSc is microangiopathic. In SSc, the blood flow is reduced in the small penile arteries due to corporal fibrosis and myointimal proliferation. There are no data on the prevention of ED in SSc. On-demand phosphodiesterase-5 inhibitors have little effect in improving erectile function, but daily or alternate day regimens of long-acting phosphodiesterase-5 inhibitors provide a measurable, although often limited, benefit. When intracavernous prostaglandin E1 injections are also ineffective, the implantation of a penile prosthesis should be considered as an option. PMID:27402106

  8. Neuropsychiatric manifestations of multiple sclerosis.

    PubMed

    Diaz-Olavarrieta, C; Cummings, J L; Velazquez, J; Garcia de la Cadena, C

    1999-01-01

    The range of neuropsychiatric symptoms in multiple sclerosis (MS) has not been prospectively assessed. The authors, working at a tertiary medical center in Mexico City, used the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms prospectively in 44 MS patients who were stable between relapses and 25 control subjects of similar age, education, and cognitive function. Neuropsychiatric symptoms were present in 95% of patients and 16% of control subjects. Changes present were depressive symptoms (79%), agitation (40%), anxiety (37%), irritability (35%), apathy (20%), euphoria (13%), disinhibition (13%), hallucinations (10%), aberrant motor behavior (9%), and delusions (7%). The only relationships with MRI were between euphoria and hallucinations and moderately severe MRI abnormalities. The authors conclude that diverse types of neuropsychiatric symptoms are common in MS; symptoms are present between exacerbations; and there are variable correlations with MRI abnormalities.

  9. Systemic sclerosis, a rare case.

    PubMed

    Sousa, Elsa; Valente, Paula; Santos, Mafalda

    2011-01-01

    Systemic sclerosis (SS) is a rare severe autoimmune disease involving the connective tissue. The pathophysiology is not clearly understood. It is characterized by a remarkable clinical heterogeneity, and virtually all organs can be affected. Concerning diagnosis, the presence of antinuclear antibodies (ANA) can be found in more than 90% of patients, but the diagnosis is made gathering clinical manifestations, autoimmune panel, nailfold capillaroscopy and in some cases biopsy of the organ involved. The disease course is also weakly understood, although some serological patterns can be distinguished. Current therapeutic options target few aspects of pathologic mechanism and clinical management remains a challenge.The authors presented a rare case of a SS ANA negative, which demonstrates the diagnostic challenge of this disease.

  10. Audiovestibular involvement in systemic sclerosis.

    PubMed

    Berrettini, S; Ferri, C; Pitaro, N; Bruschini, P; Latorraca, A; Sellari-Franceschini, S; Segnini, G

    1994-01-01

    In order to evaluate the nature and association of audiovestibular disturbances and systemic sclerosis (SSC), 37 unselected SSC patients were studied with a detailed audiological and vestibular examination since November, 1987. Pure-tone audiometry, speech audiometry, impedance audiometry, brainstem response audiometry and vestibular function using electronystagmographic recording were performed. We found a rather frequent audiovestibular involvement (41%). A hearing loss was found in 14 SSC patients; hearing loss was sensorineural in 10 cases and mixed in 4 cases. The latter revealed a finding similar to tympanosclerosis. Four patients showed altered vestibular test values and only one of these had normal hearing. Sensorineural deafness was the more frequent pathological finding and in all cases the site of lesion was cochlear. SSC appears to be directly responsible for audiovestibular damage, since in 12 out of 15 patients with such involvement, no other apparent cause could be revealed. SSC may be included among the autoimmune diseases which may cause audiovestibular disturbances. PMID:8078672

  11. Hughes syndrome and multiple sclerosis.

    PubMed

    Uthman, I; Noureldine, M H A; Berjawi, A; Skaf, M; Haydar, A A; Merashli, M; Hughes, G R V

    2015-02-01

    Multiple sclerosis (MS) and antiphospholipid syndrome (APS) share common clinical, laboratory and radiological features. We reviewed all the English papers on MS and APS published in the literature from 1965 to 2014 using PubMed and Google Scholar. We found that APS can mimic antiphospholipid antibodies (aPL)-positive MS in many ways in its clinical presentation. Nevertheless, APS diagnosis, clinical manifestations and management differ from those of MS. aPL were found in MS patients with titers ranging from 2% to 88%. The distribution and volume of lesions on magnetic resonance imaging (MRI) may help to differentiate MS from primary APS. In addition, atypical MS presentation can guide physicians toward an alternative diagnosis, especially when features of thrombosis and/or history of connective tissue disease are present. In that case, an anticoagulation trial could be worthwhile. PMID:25326228

  12. Vision Disturbances in Multiple Sclerosis.

    PubMed

    Costello, Fiona

    2016-04-01

    Visual disturbances are frequently encountered in multiple sclerosis (MS), and include problems with how affected individuals see the world (afferent visual pathway symptoms) and how their eyes move together (efferent visual pathway disorders). Optic neuritis is the most common afferent visual pathway manifestation of MS, from which visual recovery is often incomplete. Visual field defects caused by lesions in the retrochiasmal or retrogeniculate regions of the afferent visual pathway also occur, albeit less frequently. Efferent visual pathway lesions causing ocular misalignment and nystagmus may lead to diplopia and oscillopsia, respectively. Vision loss has a major impact on perceptions regarding quality of life in MS. Therefore, it is important for clinicians to be able to identify and localize the underlying basis of visual disturbances to provide the best care possible for their patients. PMID:27116725

  13. Personality aspects in multiple sclerosis.

    PubMed

    Diana, R; Grosz, A; Mancini, E

    1985-12-01

    To test the claim that peculiar personality bias is detectable in multiple sclerosis (MS) we used the Szondi test to investigate the psychodynamic aspects of 110 MS patients in comparison with 200 healthy subjects. MS patients appeared to have a greater need for love in a passive form than normal people, rigid defense mechanisms, difficulty in resolving their inner conflicts either by sublimation or by internalization of satisfactory new emotional experiences, feelings of autoaggressiveness, and many symptoms of depression. Some of these aspects correlate with the severity of the disease, others seem to date back to early childhood as peculiar personality patterns. An investigation of childhood events in 110 controls confirmed that MS patients had had many more unhappy experiences in childhood than might commonly be expected. Further, the oft-reported psychiatric troubles preceding MS clinical onset suggest that at least in some MS patients there are specific gaps in personality structure dating back to early phases of their development. PMID:4086262

  14. [Cognitive Impairment in Multiple Sclerosis].

    PubMed

    Niino, Masaaki; Miyazaki, Yusei

    2016-04-01

    While cognitive impairment is a major symptom of multiple sclerosis (MS), it is commonly overlooked. This may be explained by the fact that it is difficult to evaluate cognitive function in patients with MS using screening batteries for the detection of dementia such as the mini-mental state examination. Further more, cognitive impairment in MS typically involves domain-specific deficits such as imparement of sustained attention and information processing speed rather than global cognitive decline. Cognitive impairment may influence the daily living and social lines of affected patients. This review discusses the characteristics of cognitive impairment, appropreate tests to evaluate its symptoms, and the current status of clinical trials for the treatment of MS. PMID:27056855

  15. Autonomic Dysregulation in Multiple Sclerosis

    PubMed Central

    Pintér, Alexandra; Cseh, Domonkos; Sárközi, Adrienn; Illigens, Ben M.; Siepmann, Timo

    2015-01-01

    Multiple sclerosis (MS) is a chronic, progressive central neurological disease characterized by inflammation and demyelination. In patients with MS, dysregulation of the autonomic nervous system may present with various clinical symptoms including sweating abnormalities, urinary dysfunction, orthostatic dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic disturbances reduce the quality of life of affected patients and constitute a clinical challenge to the physician due to variability of clinical presentation and inconsistent data on diagnosis and treatment. Early diagnosis and initiation of individualized interdisciplinary and multimodal strategies is beneficial in the management of autonomic dysfunction in MS. This review summarizes the current literature on the most prevalent aspects of autonomic dysfunction in MS and provides reference to underlying pathophysiological mechanisms as well as means of diagnosis and treatment. PMID:26213927

  16. [Emerging therapies for multiple sclerosis].

    PubMed

    de Lorenzo-Pinto, Ana; Rodríguez-González, Carmen Guadalupe; Ais-Larisgoitia, Arantza

    2013-01-19

    Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system considered the second cause of disability in young adults. The prognosis of MS has improved significantly since the approval of the first interferon β in 1993 but, compared to other diseases, few new therapeutic products have been commercialized in the last years. However, currently, there are more than 600 ongoing clinical trials and new drugs that aim to improve efficacy and a more convenient schedule of administration, will appear shortly on the market. On the other hand, new safety issues will arise as well as a significant economic impact on the health system. The main efficacy and safety results of these drugs are reviewed in this paper. They can be classified into 2 groups: oral (fingolimod, laquinimod, teriflunomide, BG-12 [dimethyl fumarate], oral cladribine, dalfampridine) and monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab). PMID:22766059

  17. Oral agents in multiple sclerosis.

    PubMed

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  18. [Current immunotherapy of multiple sclerosis].

    PubMed

    Paul, F; Ruprecht, K

    2015-08-01

    Following the introduction of interferon beta 1b as the first immunomodulatory therapy for multiple sclerosis (MS) in 1993, there are currently nine substances or substance classes approved for the treatment of MS (i.e. alemtuzumab, azathioprine, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab and teriflunomide). Major developments during the last 5 years include the approval of orally administered medications (i.e. fingolimod, teriflunomide and dimethyl fumarate), a monoclonal antibody (alemtuzumab), as well as glatiramer acetate with an administration frequency three times a week and a pegylated formulation of interferon beta 1a. The broadened therapeutic options enable a more differentiated and individualized therapy of MS; however, evidence-based data for therapeutic decision-making relevant in clinical practice are not always available. Rare but potentially severe and even life-threatening side effects of immunotherapies for MS require continuous pharmacovigilance and adherence to risk management plans. PMID:26253589

  19. 2014 multiple sclerosis therapeutic update.

    PubMed

    Cree, Bruce A C

    2014-04-01

    Rapid advances are occurring in multiple sclerosis disease modifying therapies. Recent therapeutic advances include modifications to improve tolerability of existing products (e.g. interferon beta and glatiramer acetate), development of novel anti-neuroinflammatory medications (e.g. fingolimod, teriflunomide and dimethyl fumarate, daclizumab, alemtuzumab, ocrelizumab) and investigation of treatments in progressive MS (e.g. natalizumab, mastinib, natalizumab, siponimod). The impact of vitamin D supplementation on the disease course in relapsing MS patients is also being studied in several clinical trials. This article reviews the current state of the field with a forward look to the next phase of MS research that could focus on strategies to promote remyelination and provide neuronal protection. PMID:24707333

  20. Immunological treatment of multiple sclerosis.

    PubMed

    Diebold, Martin; Derfuss, Tobias

    2016-04-01

    Treatment of multiple sclerosis (MS) has been a challenge since its first description by Charcot. The advent of immunomodulatory drugs in the mid 1990s brought the first big change in the treatment of MS patients. During the last 10 years there has been an ongoing tremendous evolution of novel treatment options for relapsing-remitting MS. These options include monoclonal antibodies, which inhibit migration of lymphocytes (natalizumab), deplete lymphocytes (alemtuzumab), or block the cytokine receptor interleukin (IL)-2 (daclizumab), teriflunomide that inhibits proliferation of activated lymphocytes, fingolimod that modulates the sphingosine-receptor system, and dimethylfumarate that combines features of immunomodulatory and immunosuppressive drugs. The topic of this review is to discuss currently available treatments and provide an outlook into the near future. PMID:27312167

  1. Orofacial manifestations of systemic sclerosis.

    PubMed

    Veale, B J; Jablonski, R Y; Frech, T M; Pauling, J D

    2016-09-23

    Systemic sclerosis (SSc) is a multisystem disease of unknown aetiology characterised by microangiopathy, dysregulated immune function and tissue remodelling, which commonly involves the oral cavity. Orofacial manifestations of SSc contribute greatly to overall disease burden and yet are regularly overlooked and under-treated. This may reflect a pre-occupation amongst rheumatology clinicians on potentially life-threatening internal organ involvement, but is also a consequence of insufficient engagement between rheumatologists and dental professionals. A high proportion of SSc patients report difficulty accessing a dentist with knowledge of the disease and there is recognition amongst dentists that this could impact negatively on patient care. This review shall describe the clinical features and burden of orofacial manifestations of SSc and the management of such problems. The case is made for greater collaborative working between rheumatologists and dental professionals with an interest in SSc in both the research and clinical setting. PMID:27659631

  2. Progress in Multiple Sclerosis Genetics

    PubMed Central

    Goris, An; Pauwels, Ine; Dubois, Bénédicte

    2012-01-01

    A genetic component in the susceptibility to multiple sclerosis (MS) has long been known, and the first and major genetic risk factor, the HLA region, was identified in the 1970’s. However, only with the advent of genome-wide association studies in the past five years did the list of risk factors for MS grow from 1 to over 50. In this review, we summarize the search for MS risk genes and the latest results. Comparison with data from other autoimmune and neurological diseases and from animal models indicates parallels and differences between diseases. We discuss how these translate into an improved understanding of disease mechanisms, and address current challenges such as genotype-phenotype correlations, functional mechanisms of risk variants and the missing heritability. PMID:23730204

  3. Vitamin D and multiple sclerosis.

    PubMed

    Harandi, Asghar Amini; Harandi, Ali Amini; Pakdaman, Hossein; Sahraian, Mohammad Ali

    2014-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disease and also is one of the most common disabling neurological disorders in young and middle-aged adults. The main pathogenesis of MS has long been thought to be an immune mediated disorder of the central nervous system. The function of the immune system is under the influence of vitamin D which as a modulator of immune response could play a role in autoimmune diseases including MS. Deficiency of vitamin D or variations in DNA sequence (polymorphism) of vitamin D receptor gene diminishes its optimal function on immune system that consequently could lead to increasing risk of MS. However, its role in development and modulating the course of MS is still under investigation. In this review we aimed to discuss the role of vitamin D in body, immune system and consequently altering the risk of MS. PMID:24800040

  4. Vitamin D and multiple sclerosis

    PubMed Central

    Harandi, Ali Amini; Pakdaman, Hossein; Sahraian, Mohammad Ali

    2014-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disease and also is one of the most common disabling neurological disorders in young and middle-aged adults. The main pathogenesis of MS has long been thought to be an immune mediated disorder of the central nervous system. The function of the immune system is under the influence of vitamin D which as a modulator of immune response could play a role in autoimmune diseases including MS. Deficiency of vitamin D or variations in DNA sequence (polymorphism) of vitamin D receptor gene diminishes its optimal function on immune system that consequently could lead to increasing risk of MS. However, its role in development and modulating the course of MS is still under investigation. In this review we aimed to discuss the role of vitamin D in body, immune system and consequently altering the risk of MS. PMID:24800040

  5. Care Partners and Multiple Sclerosis

    PubMed Central

    Quig, Mary Elizabeth; Tyry, Tuula; Marrie, Ruth Ann; Cutter, Gary; Shearin, Edward; Johnson, Kamau; Simsarian, James

    2015-01-01

    Background: Caring for someone with multiple sclerosis (MS) can be a stressful experience that requires clinical attention. We investigated the impact of caregiver stress on the emotional well-being and physical health of the MS care partner using the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. Methods: Care partners of NARCOMS participants were invited to complete an online questionnaire that captured demographic characteristics, health status, caregiver burden as measured by the Zarit Caregiver Burden Interview, and impact of caregiving on employment. Results: Of 1446 care partners who agreed to participate, 1333 had complete data. Most were men (n = 825, 61.9%), with a mean (SD) age of 51.1 (11.2) years. The mean (SD) Zarit total score was 24.6 (15.1), placing the overall group in the mild caregiver burden range. Compared with male care partners, female care partners reported higher levels of burden and stress and more medication use for stress/anxiety and mood disorders. Male care partners were more likely to report physical concerns. Care partners of people with primary progressive MS reported greater perceived burden than did partners of people with secondary progressive MS and relapsing-remitting MS. More than 40% of care partners (559 of 1288) had missed work during the past year owing to caregiving responsibilities. Conclusions: Care partners of people with MS have substantial physical and psychological health concerns and experience an adverse impact on employment. Future research should evaluate how to mitigate the adverse effects of caregiving and evaluate positive aspects of the role. PMID:26664330

  6. Recent developments in multiple sclerosis therapeutics.

    PubMed

    Spain, Rebecca I; Cameron, Michelle H; Bourdette, Dennis

    2009-12-07

    Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-beta, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought.

  7. Remyelination Therapy in Multiple Sclerosis

    PubMed Central

    Harlow, Danielle E.; Honce, Justin M.; Miravalle, Augusto A.

    2015-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients. PMID:26696956

  8. Tuberous Sclerosis Complex: Perioperative Considerations

    PubMed Central

    Rabito, Matthew J.; Kaye, Alan David

    2014-01-01

    Background Tuberous sclerosis complex (TSC), also known as Bourneville disease, is an inherited, progressive neurocutaneous disorder characterized by the potential for hamartoma formation throughout the body. TSC is an autosomal dominant genetic disorder, but more than two-thirds of cases are sporadic. Methods Clinical manifestations and treatment options are discussed. Both surgical and anesthetic perioperative considerations are described in this review. Results Routine monitoring is appropriate for minor surgical procedures for patients with TSC who have mild disease manifestations. More extensive monitoring is indicated for major procedures that have the potential for significant blood loss and for patients with more severe pathology. Postoperatively, TSC patients should be admitted for monitoring and treatment after more extensive procedures or if significant organ dysfunction occurs. Postoperative complications, which may be related to either the surgery or the TSC pathology itself, may have origins in many different organs and may include seizures, severe hypertension, and bradyarrhythmias. Conclusion TSC is a rare disease with a highly variable clinical presentation and provides a multitude of challenges for the patient, the family, and the healthcare team. PMID:24940133

  9. [Oral treatments in multiple sclerosis].

    PubMed

    Meca-Lallana, José Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

    2014-12-01

    The development of new disease-modifying drugs (DMD) in relapsing-remitting multiple sclerosis (RRMS), which share the common denominator of oral administration, considerably improves patient expectations in terms of effectiveness, tolerability and treatment adherence compared with currently available drugs. However, the common route of administration of these drugs does not mean that they are equivalent, since the heading of "oral route" encompasses drugs with distinct indications and mechanisms of action, as well as heterogeneous results in terms of efficacy and safety, allowing treatment to be personalized according to the each patient' s characteristics. Currently, four oral DMD are available or in an advanced stage of clinical development: fingolimod, teriflunomide, dimethyl fumarate and laquinimod. In pivotal trials versus placebo, these molecules reduced the annualized rate of exacerbations versus placebo by 54%, 31%, 53% and 23%, respectively, the risk of progression of disability by 31%, 30%, 38% and 36%, and the number of active lesions showing contrast uptake on magnetic resonance imaging by 82%, 80%, 90% and 37%, respectively. Based on the risk/benefit ratio, fingolimod is indicated in patients with suboptimal response to initial DMD or in severe rapidly progressing RRMS, while the remaining drugs can be used as first-line options. Clinical experience with these treatments will provide new data on safety and effectiveness, which will be determinant when establishing therapeutic algorithms. PMID:25732946

  10. Cardiovascular dysfunction in multiple sclerosis.

    PubMed

    Acevedo, A R; Nava, C; Arriada, N; Violante, A; Corona, T

    2000-02-01

    Cardiovascular dysfunction (CD) in multiple sclerosis (MS) is related to involvement of reflex pathways in the brainstem. The battery of CD tests was applied to a group of 40 healthy subjects and 40 patients with MS, divided in 2 subgroups according to the expanded disability status scale (EDSS). The tests included: 1) postural blood pressure changes, 2) postural heart rate changes, 3) heart rate changes on inspiration/forced expiration and 4) ECG R-R interval measurement on the Valsalva maneuver. Both groups were subjected to the functional independence scale (FIM). Imaging studies were reviewed and autonomic dysfunction at other levels was explored. The results showed a statistically significant difference (P < 0.05) in all tests when comparing patients to controls. Tests 1 and 4 had the highest significance, with findings of more severe involvement in patients with a higher EDSS and lower FIM. A correlation was also found between CD and brainstem lesions on MRI (P < 0.01). A significant number of MS patients had evidence of CD. Test 1 may be considered a simple marker, in daily clinical practice, to detect subclinical CD. Subclinical CD is a cause of disability in this group of patients.

  11. Remyelination Therapy in Multiple Sclerosis.

    PubMed

    Harlow, Danielle E; Honce, Justin M; Miravalle, Augusto A

    2015-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.

  12. Cardiovascular disease in systemic sclerosis

    PubMed Central

    Cannarile, Francesca; Valentini, Valentina; Mirabelli, Giulia; Alunno, Alessia; Terenzi, Riccardo; Luccioli, Filippo; Bartoloni, Elena

    2015-01-01

    Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc. PMID:25705640

  13. Multiple sclerosis: Prospects and promise.

    PubMed

    Hauser, Stephen L; Chan, Jonah R; Oksenberg, Jorge R

    2013-09-01

    We have entered a golden era in multiple sclerosis (MS) research. Two decades ago, our understanding of the disease was largely descriptive and there were no approved therapies to modify the natural history of MS. Today, delineation of immune pathways relevant to MS have been clarified; a comprehensive map of genes that influence risk compiled; clues to environmental triggers identified; noninvasive in vivo monitoring of the MS disease process has been revolutionized by high-field MRI; and many effective therapies for the early, relapsing, component of MS now exist. However, major challenges remain. We still have no useful treatment for progressive MS (the holy grail of MS research), no means to repair injured axons or protect neurons, and extremely limited evidence to guide treatment decisions. Recent advances have set in place a foundation for development of increasingly selective immunotherapy for patients; application of genetic and genomic discoveries to improve therapeutic options; development of remyelination or neuroprotection therapies for progressive MS; and integrating clinical, imaging and genomic data for personalized medicine. MS has now advanced from the backwaters of autoimmune disease research to the front-line, and definitive answers, including cures, are now realistic goals for the next decade. Many of the breakthrough discoveries in MS have also resulted from meaningful interactions across disciplines, and especially from translational and basic scientists working closely with clinicians, highlighting that the clinical value of discoveries are most often revealed when ideas developed in the laboratory are tested at the bedside. PMID:23955638

  14. Endothelin-1 in systemic sclerosis

    PubMed Central

    Aghaei, Mehrdad; Gharibdost, Farhad; Zayeni, Habib; Akhlaghi, Maryam; Sedighi, Sima; Rostamian, Abduo Rahman; Aghdami, Naser; Shojaa, Mahdieh

    2012-01-01

    Introduction: Scleroderma is a systemic disorder with unknown etiology most notably characterized by skin thickening and organ damage. Endothelin-1 (ET-1) plays a role in skin fibrosis. The aim of this study was survey and comparison of ET-1 level in Systemic Sclerosis (SSc) patients with and without digital ulcer. Material and Methods: A cross-sectional analytical study conducted among the 95 patients with scleroderma in 2006 who were referred to the Rheumatology clinic in Shariati hospital of Tehran. The questionnaire was completed for every patient. Plasma level of endothelin-1 was also measured in all of them. The data was analyzed using SPSS software and statistical tests. Results: The result indicated, relationship among digital ulcers and digital pitting scars with plasma level of ET-1 were significant (P value < 0.05). We could not find any significant relationship between age and plasma level of ET-1. Conclusion: These data indicate plasma level of ET-1 in scleroderma patients with digital ulcer was higher than patients without digital ulcer. Thus, increase in plasma level of ET-1 could be effective in vascular damage, fibrosis, and skin thickness. PMID:23130253

  15. Role of Chlamydia in Multiple Sclerosis.

    PubMed

    Ivanova, M V; Kolkova, N I; Morgunova, E Yu; Pashko, Yu P; Zigangirova, N A; Zakharova, M N

    2015-09-01

    Chlamydia and antibodies to them were detected by serological, molecular biological, and culture methods in the sera and cerebrospinal fluid of patients with multiple sclerosis and in the reference groups of subjects without neurological diseases. Correlations between the agent presence in the biological fluids of patients and clinical characteristics of the disease were analyzed. C. pneumoniae were more incident in the biological liquids of patients with multiple sclerosis than in healthy volunteers. On the other hand, the incidence of the agent in the patients was not high and its presence did not correlate with the clinical manifestations. C. trachomatis was equally rare in the patients and volunteers. The studies indicated the existence of a group of patients infected by C. pneumoniae in the cohort of patients with multiple sclerosis, but the impact of this agent for the disease course remains unclear.

  16. Current and future therapies for multiple sclerosis.

    PubMed

    Minagar, Alireza

    2013-01-01

    With the introduction of interferon- β 1b in 1993 as the first FDA-approved treatment for multiple sclerosis, the era of treatment of this incurable disease began, and its natural course was permanently changed. Currently, seven different treatments for patients with multiple sclerosis with different mechanisms of action and dissimilar side effect profiles exist. These medications include interferon- β 1a intramuscular (Avonex), interferon- β 1a subcutaneous (Rebif), interferon- β 1b subcutaneous (Betaseron/Extavia), glatiramer acetate (Copaxone), natalizumab (Tysabri), fingolimod (Gilenya), teriflunomide (Aubagio), and mitoxantrone (Novantrone). In addition, a large number of clinical trials are being conducted to assess the safety and efficacy of various experimental agents in patients with multiple sclerosis, including alemtuzumab, dimethyl fumarate, laquinimod, rituximab, daclizumab, and cladribine. In this paper, the author presents a concise and comprehensive review of present and potential treatments for this incurable disease. PMID:24278770

  17. [Clinical picture and epidemiology of disseminated sclerosis].

    PubMed

    Popov, V S

    1983-01-01

    The prevalence and characteristic features of the clinical course of disseminated sclerosis in the population of the Far North were studied. The proportion of disseminated sclerosis among organic diseases of the central nervous system in this area is considerably lower (0.36%) than in many regions and areas of Western and Eastern Siberia and especially in the central regions of the European part of the USSR. A considerable difference in the incidence of this disease between the local population and newcomers is noted, namely 7% and 93%, respectively. Local population displays a more progressive course of the disease. No cases of disseminated sclerosis have been recorded among the indigenous population i.e., yakutes and small nationalities of the North.

  18. Mental disorders in Mexican patients with multiple sclerosis.

    PubMed

    Espinola-Nadurille, Mariana; Colin-Piana, Ricardo; Ramirez-Bermudez, Jesus; Lopez-Gomez, Mario; Flores, Jose; Arrambide, Georgina; Corona, Teresa

    2010-01-01

    The authors aim to explore psychiatric disorders in Mexican patients with multiple sclerosis. The Structured Clinical Interview for DSM-IV Axis I Disorders, the Montgomery-Asberg Depression Rating Scale, and the Hamilton Anxiety Rating Scale were administered to 37 consecutive multiple sclerosis patients and 37 healthy comparison subjects. The multiple sclerosis group had higher rates of any axis I disorder (OR 1.97; 95% CI=1.78-3.306). The most common comorbid diagnoses were depressive disorders (46% of the multiple sclerosis cases) with higher anxiety scores (p=0.001). No correlations between psychiatric variables, number of relapses, and clinical course of multiple sclerosis were found.

  19. Emerging therapies for treatment of multiple sclerosis

    PubMed Central

    Corboy, John R; Miravalle, Augusto A

    2010-01-01

    In the last decade, a new armamentarium of immune-based therapies have been developed and tested in patients with multiple sclerosis. Some of these therapies are showing a high level of efficacy, with an acceptable adverse effect profile. Because present therapies have significant limitations in slowing disease progression, require injections, are sometimes associated with significant side effects of immunosuppression, and do little to reverse disability, identifying more effective treatments is an important goal for clinical research in multiple sclerosis. However, in order to improve our current approach to disease-modifying therapies, it is imperative to promote the development of individualized therapy strategies. PMID:22096357

  20. [Large vessels vasculopathy in systemic sclerosis].

    PubMed

    Tejera Segura, Beatriz; Ferraz-Amaro, Iván

    2015-12-01

    Vasculopathy in systemic sclerosis is a severe, in many cases irreversible, manifestation that can lead to amputation. While the classical clinical manifestations of the disease have to do with the involvement of microcirculation, proximal vessels of upper and lower limbs can also be affected. This involvement of large vessels may be related to systemic sclerosis, vasculitis or atherosclerotic, and the differential diagnosis is not easy. To conduct a proper and early diagnosis, it is essential to start prompt appropriate treatment. In this review, we examine the involvement of large vessels in scleroderma, an understudied manifestation with important prognostic and therapeutic implications. PMID:25726305

  1. Tuberous sclerosis complex: A case report

    PubMed Central

    Sarkar, Soumyabrata; Khaitan, Tanya; Sinha, Rupam; Kabiraj, Arpita

    2016-01-01

    Tuberous sclerosis complex is an unusual autosomal dominant neurocutaneous syndrome characterized by the development of benign tumors affecting different body systems affecting the brain, skin, retina, and viscera. It is characterized by cutaneous changes, neurologic conditions, and the formation of hamartomas in multiple organs leading to morbidity and mortality. The most common oral manifestations are fibromas, gingival hyperplasia, and enamel hypoplasia. The management of these patients is often multidisciplinary involving specialists from various fields. Here, we present a case report of a 26-old-year male patient with characteristic clinical, radiological, and histological features of tuberous sclerosis complex. PMID:27307675

  2. Electroconvulsive therapy in patients with multiple sclerosis.

    PubMed

    Rasmussen, Keith G; Keegan, B Mark

    2007-09-01

    There are relatively few case reports of electroconvulsive therapy (ECT) in patients with multiple sclerosis. We present 3 such patients, all of whom received safe, effective ECT without evidence of acute neurological deterioration. We conclude that patients with multiple sclerosis being considered for ECT should have a thorough neurological evaluation, and the informed consent process should include discussion of the possibility of neurological deterioration. However, review of the literature and of our 3 cases does reveal that ECT can be used safely, at least in the short term. Long-term outcomes in such patients remain uncertain.

  3. Single fibre electromyographic jitter in multiple sclerosis.

    PubMed Central

    Weir, A; Hansen, S; Ballantyne, J P

    1979-01-01

    Recent histological and electrophysiological reports have given evidence for peripheral nervous system (PNS) involvement in multiple sclerosis. We have applied the single fibre electromyography (SFEMG) technique to 15 patients with multiple sclerosis. Six patients had clearly abnormal jitter and two of these had previously undiagnosed coexistent peripheral neuropathy. A further five patients had borderline abnormalities of SFEMG. The mean jitter for each patient was abnormal in 10 patients. This was clear evidence for PNS involvement in this disease. Theoretically, the site of the abnormality could be in the terminal nerve network or at the neuromuscular junction, but this technique cannot distinguish between these sites. PMID:533854

  4. Amyotrophic Lateral Sclerosis: A Historical Perspective.

    PubMed

    Katz, Jonathan S; Dimachkie, Mazen M; Barohn, Richard J

    2015-11-01

    This article looks back in time to see where the foundational basis for the understanding of amyotrophic lateral sclerosis originated. This foundation was created primarily in France by Jean-Martin Charcot and his fellow countrymen and disciples, along with key contributions from early clinicians in England and Germany. The early work on amyotrophic lateral sclerosis provides a useful foundation for today's clinicians with respect to tying together genetic and biologic aspects of the disorder that have been discovered over the past few decades.

  5. Iron chelation and multiple sclerosis

    PubMed Central

    Weigel, Kelsey J.; Lynch, Sharon G.; LeVine, Steven M.

    2014-01-01

    Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen. PMID:24397846

  6. Defective immunoregulation in multiple sclerosis.

    PubMed

    Goust, J M; Hoffman, P M; Pryjma, J; Hogan, E L; Fudenberg, H H

    1980-11-01

    Imbalances in T cell subpopulations have been reported in multiple sclerosis (MS). In the present study of 31 MS patients, the percentage of T cells with Fc receptors for IgG (Tg) was found to be increased in patients with chronic progressive disease, and another T cell subset binding to the Raji B lymphoid cell line was decreased. An inverse correlation (r = -0.675; < 95% confidence limit) was found between these two subsets, suggesting that they vary inversely in MS. The mitogenic responses of MS mononuclear cells, isolated T cells, and recombinet T and non-T cells to the lectins phytohemagglutinin and pokeweek mitogen (PWM) did not differ from those of normal cells. However, more immunoglobulin (Ig)-producing cells were generated in a PWM-driven system with cells from MS patients than with cells from age-matched controls (p < 0.05). Autologous recombination of separated T and non-T cells did not significantly modify these results. T cells from MS patients added to B cells from normal controls exerted an effect that was related to their percentage of Tg cells; that is, values above 15% were associated with a suppression of Ig production, whereas for Tg values below 12%, a helper effect or no modification was observed. These results suggest that changes in T cell subsets in MS are related to changes in functional ability to modulate Ig production by normal B cells. However, MS B cells partly escape regulation by their own T cells, suggesting an associated B cell hyperactivity. PMID:7436394

  7. Taste dysfunction in multiple sclerosis.

    PubMed

    Doty, Richard L; Tourbier, Isabelle A; Pham, Dzung L; Cuzzocreo, Jennifer L; Udupa, Jayaram K; Karacali, Bilge; Beals, Evan; Fabius, Laura; Leon-Sarmiento, Fidias E; Moonis, Gul; Kim, Taehoon; Mihama, Toru; Geckle, Rena J; Yousem, David M

    2016-04-01

    Empirical studies of taste function in multiple sclerosis (MS) are rare. Moreover, a detailed assessment of whether quantitative measures of taste function correlate with the punctate and patchy myelin-related lesions found throughout the CNS of MS patients has not been made. We administered a 96-trial test of sweet (sucrose), sour (citric acid), bitter (caffeine) and salty (NaCl) taste perception to the left and right anterior (CN VII) and posterior (CN IX) tongue regions of 73 MS patients and 73 matched controls. The number and volume of lesions were assessed using quantitative MRI in 52 brain regions of 63 of the MS patients. Taste identification scores were significantly lower in the MS patients for sucrose (p = 0.0002), citric acid (p = 0.0001), caffeine (p = 0.0372) and NaCl (p = 0.0004) and were present in both anterior and posterior tongue regions. The percent of MS patients with identification scores falling below the 5th percentile of controls was 15.07 % for caffeine, 21.9 % for citric acid, 24.66 % for sucrose, and 31.50 % for NaCl. Such scores were inversely correlated with lesion volumes in the temporal, medial frontal, and superior frontal lobes, and with the number of lesions in the left and right superior frontal lobes, right anterior cingulate gyrus, and left parietal operculum. Regardless of the subject group, women outperformed men on the taste measures. These findings indicate that a sizable number of MS patients exhibit taste deficits that are associated with MS-related lesions throughout the brain. PMID:26810729

  8. Retroviruses and amyotrophic lateral sclerosis

    PubMed Central

    Alfahad, Tariq; Nath, Avindra

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive, invariably fatal neurologic disorder resulting from upper and lower motor neuron degeneration, which typically develops during the sixth or seventh decade of life, and is diagnosed based on standard clinical criteria. Its underlying cause remains undetermined. The disease may occur with increased frequency within certain families, often in association with specific genomic mutations, while some sporadic cases have been linked to environmental toxins or trauma. Another possibility, first proposed in the 1970s, is that retroviruses play a role in pathogenesis. In this paper, we review the published literature for evidence that ALS is associated either with infection by an exogenous retrovirus or with the expression of human endogenous retroviral (HERV) sequences in cells of the central nervous system. A small percentage of persons infected with the human immunodeficiency virus-1 (HIV-1) or human T cell leukemia virus-1 (HTLV-1) develop ALS-like syndromes. While HTLV-1 associated ALS-like syndrome has several features that may distinguish it from classical ALS, HIV-infected patients may develop neurological manifestations that resemble classical ALS although it occurs at a younger age and they may show a dramatic improvement following the initiation of antiretroviral therapy. However, most patients with probable or definite ALS show no evidence of HIV-1 or HTLV-1 infection. In contrast, recent reports have shown a stronger association with HERV, as analysis of serum samples, and postmortem brain tissue from a number of patients with a classical ALS has revealed significantly increased expression of HERV-K, compared to controls. These findings suggest that endogenous retroviral elements are involved in the pathophysiology of ALS, but there is no evidence that they are the primary cause of the syndrome. PMID:23707220

  9. Nutrition Facts in Multiple Sclerosis

    PubMed Central

    Rossano, Rocco

    2015-01-01

    The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness. PMID:25694551

  10. Nutrition facts in multiple sclerosis.

    PubMed

    Riccio, Paolo; Rossano, Rocco

    2015-01-01

    The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.

  11. Nutrition facts in multiple sclerosis.

    PubMed

    Riccio, Paolo; Rossano, Rocco

    2015-01-01

    The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness. PMID:25694551

  12. Early prognosis of multiple sclerosis.

    PubMed

    Swanton, Josephine; Fernando, Kryshani; Miller, David

    2014-01-01

    Establishing the prognosis for multiple sclerosis (MS) early in the disease course is critically important for patients who develop this disease. Potentially, this information could be used to guide the selection of which disease modifying therapy (if any) should be started in which individual and to determine, over course of the illness, when the therapeutic approach needs to be modified. Regardless, of its importance, however, we only have a limited ability to predict how an individual's illness will evolve. For several decades, we have known about certain clinical features of MS that seem to associated with a more benign course (e.g., female gender, clinical onset before the age of 40 years, few early relapses, slow early accumulation of fixed deficits, and the initial involvement of only sensory systems). Nevertheless, the prognostic value of these clinical features offer only limited help to individual patients in making their different (and difficult) life-choices. For this reason, there have been numerous attempts to develop paraclinical tests, which can augment (and improve upon) this clinical prognostic information. These approaches have included the use of magnetic resonance imaging (MRI) measures such as gadolinium enhancement, new T2 lesions, the volume of T2 lesion burden, brain atrophy (either whole brain or separately for grey and white matter), spinal cord atrophy, cortical connectivity, and determining the characteristics and chemical composition of the normal appearing white matter. They have also included investigations of the use of immunological markers for establishing prognosis. Nevertheless, this field is still only in its infancy and our ability to predict accurately the outlook for an individual remains limited at best. This chapter reviews the current evidence, taken from both clinical and paraclinical sources, as it relates to establishing this prognosis and provides insight to where, in the future, we need to look. PMID:24507526

  13. Pancreatic necrosis in progressive systemic sclerosis.

    PubMed Central

    Abraham, A A; Joos, A

    1980-01-01

    Fatal pancreatic necrosis, secondary to extensive acute arteritic changes, is reported in a case of progressive systemic sclerosis. The patient presented first with hypertension and renal involvement, with active vascular lesions demonstrated by biopsy. The renal lesion at necropsy was inactive, showing the characteristic concentric fibrosis only, while the pancreatic vascular lesions were both chronic proliferative and acute in type. Images PMID:7436566

  14. Magnetic resonance sees lesions of multiple sclerosis

    SciTech Connect

    Ziporyn, T.

    1985-02-15

    The value of nuclear magnetic resonance imaging in the diagnosis and quantitation of the progression of multiple sclerosis is discussed. Magnetic resonance imaging generates images that reflect differential density and velocity of hydrogen nuclei between cerebral gray and white matter, as well as between white matter and pathological lesions of the disease.

  15. The outlook for alemtuzumab in multiple sclerosis.

    PubMed

    Williams, Thomas; Coles, Alasdair; Azzopardi, Laura

    2013-06-01

    Alemtuzumab is a humanized anti-CD52 monoclonal antibody. Treatment in humans results in a rapid, profound, and prolonged B- and T-cell lymphopenia. Subsequently, lymphocyte reconstitution by homeostatic mechanisms alters the composition, phenotype, and function of T-cell subsets, thus allowing the immune system to be 'reset'. One phase II and two phase III randomized, multicenter, single-blinded (outcomes assessor) clinical trials of alemtuzumab in relapsing-remitting multiple sclerosis have now been completed. Against an active comparator and the current first-line therapy for relapsing-remitting multiple sclerosis (interferon-beta), alemtuzumab showed a significant reduction in annualized relapse rate as well as a significant reduction in the accumulation of disability. These outcomes are sustained over at least 5 years following treatment. The most common adverse effects are mild infusion reactions, an increased incidence of mild-to-moderate severity infections and secondary autoimmunity. The latter is observed in a third of treated patients, commonly thyroid disease but other target cells have been described including cytopenias. Marketing authorization applications have been submitted for the use of alemtuzumab in multiple sclerosis to the Food and Drug Administration and the European Medicines Agency, with licensing expected in 2013. Here, we discuss the outlook for alemtuzumab in multiple sclerosis in light of the currently available therapies, outcomes of and lessons learnt from clinical trials, and the overall position of monoclonal antibodies in modern treatment strategies. PMID:23558379

  16. An Unusual Case of Perinatal Tuberous Sclerosis

    PubMed Central

    Hegde, Deeparaj Ganapati; Mondkar, Jayashree; Panchal, Harshad

    2014-01-01

    We report a case of a neonate who presented to us with multiple rhabdomyomas of heart, cortical tubers in the brain and skeletal anomalies such as Pierre Robin sequence, bilateral clubfoot and lower small bowel obstruction. Though a diagnosis of neonatal tuberous sclerosis was made, the association of skeletal anomalies and intestinal obstruction was a rare and unusual finding. PMID:25024981

  17. ▼Teriflunomide for multiple sclerosis.

    PubMed

    2014-07-01

    ▼Teriflunomide (Aubagio-Genzyme Therapeutics), the main metabolite of the disease-modifying anti-rheumatic drug leflunomide,1 is an immunomodulatory agent with anti-inflammatory properties.2 It is a new oral treatment licensed for adults with relapsing-remitting multiple sclerosis. Here we discuss the evidence for its effectiveness and safety, and consider its place in therapy. PMID:25012149

  18. Fructose Malabsorption in Systemic Sclerosis.

    PubMed

    Marie, Isabelle; Leroi, Anne-Marie; Gourcerol, Guillaume; Levesque, Hervé; Ménard, Jean-François; Ducrotte, Philippe

    2015-09-01

    The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations

  19. Fructose Malabsorption in Systemic Sclerosis

    PubMed Central

    Marie, Isabelle; Leroi, Anne-Marie; Gourcerol, Guillaume; Levesque, Hervé; Ménard, Jean-François; Ducrotte, Philippe

    2015-01-01

    Abstract The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal

  20. Lung Volume Recruitment in Multiple Sclerosis

    PubMed Central

    Srour, Nadim; LeBlanc, Carole; King, Judy; McKim, Douglas A.

    2013-01-01

    Introduction Pulmonary function abnormalities have been described in multiple sclerosis including reductions in forced vital capacity (FVC) and cough but the time course of this impairment is unknown. Peak cough flow (PCF) is an important parameter for patients with respiratory muscle weakness and a reduced PCF has a direct impact on airway clearance and may therefore increase the risk of respiratory tract infections. Lung volume recruitment is a technique that improves PCF by inflating the lungs to their maximal insufflation capacity. Objectives Our goals were to describe the rate of decline of pulmonary function and PCF in patients with multiple sclerosis and describe the use of lung volume recruitment in this population. Methods We reviewed all patients with multiple sclerosis referred to a respiratory neuromuscular rehabilitation clinic from February 1999 until December 2010. Lung volume recruitment was attempted in patients with FVC <80% predicted. Regular twice daily lung volume recruitment was prescribed if it resulted in a significant improvement in the laboratory. Results There were 79 patients included, 35 of whom were seen more than once. A baseline FVC <80% predicted was present in 82% of patients and 80% of patients had a PCF insufficient for airway clearance. There was a significant decline in FVC (122.6 mL/y, 95% CI 54.9–190.3) and PCF (192 mL/s/y, 95% 72–311) over a median follow-up time of 13.4 months. Lung volume recruitment was associated with a slower decline in FVC (p<0.0001) and PCF (p = 0.042). Conclusion Pulmonary function and cough decline significantly over time in selected patients with multiple sclerosis and lung volume recruitment is associated with a slower rate of decline in lung function and peak cough flow. Given design limitations, additional studies are needed to assess the role of lung volume recruitment in patients with multiple sclerosis. PMID:23383293

  1. Variables associated with patient activation in persons with multiple sclerosis.

    PubMed

    Goodworth, Marie-Christine R; Stepleman, Lara; Hibbard, Judith; Johns, Lisa; Wright, Dustin; Hughes, Mary D; Williams, Mitzi J

    2016-01-01

    Identifying variables associated with patient activation in the multiple sclerosis population could serve to facilitate better multiple sclerosis self-management behaviors. Using a cross-sectional survey design, 199 participants were recruited from a multiple sclerosis center in the Southeastern United States. Depression, multiple sclerosis quality of life, and multiple Sclerosis self-efficacy were all significantly correlated with patient activation. Results of a hierarchical regression indicated that patient activation was significantly related to educational attainment, depression, and self-efficacy but not to quality of life. The results suggest several possible targets for intervention to increase patient activation, including health literacy, depression symptoms, and self-efficacy for multiple sclerosis disease management.

  2. [Therapy of day time fatigue in patients with multiple sclerosis].

    PubMed

    Zifko, Udo A

    2003-01-01

    Fatigue is the most common symptom of multiple sclerosis. 75%-90% of patients with multiple sclerosis report having fatigue, and 50%-60% describe it as the worst symptom of their disease. Fatigue is significantly associated with reduced quality of life and is also a major reason for unemployment, especially for patients with otherwise minor disability. The mechanisms underlying abnormal levels of fatigue in multiple sclerosis are poorly understood. To date, drug treatment has been only partially successful in alleviating fatigue, and effects vary widely from patient to patient. Amantadine and modafinil showed to be effective in the treatment of fatigue in some studies. Non-pharmacological management of fatigue in multiple sclerosis includes inpatient rehabilitation and endurance training. There is also evidence, that pulsing electromagnetic fields may improve fatigue associated with multiple sclerosis. This paper summarizes the recent literature on pathophysiology, diagnosis and therapy of the most common symptom of multiple sclerosis.

  3. Peripheral blood lymphocyte phenotype and function in multiple sclerosis.

    PubMed Central

    Hughes, P J; Compston, D A

    1988-01-01

    T suppressor cell function and phenotype are abnormal in patients with multiple sclerosis, especially during the chronic progressive phase but the sub-populations defined by mitogen stimulation and serological methods may not be identical. In this study, involving 45 patients with multiple sclerosis and 33 controls, there was no correlation between T suppressor function and CD8 cell phenotype in patients with multiple sclerosis or in controls. These phenotypic and functional studies cannot therefore be used interchangeably in the assessment of patients with multiple sclerosis since they provide different information about lymphocyte subpopulations. PMID:2976082

  4. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    PubMed

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  5. Mesenchymal stem cells in multiple sclerosis - translation to clinical trials.

    PubMed

    Dulamea, A

    2015-01-01

    Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by an aberrant activation of the immune system and combining demyelination with neurodegeneration. Studies on experimental models of multiple sclerosis revealed immunomodulatory and immunosuppressive properties of mesenchymal stem cells. Clinical trials using mesenchymal stem cells therapy in multiple sclerosis patients showed tolerability, safety on short term, some immunomodulatory properties reducing the Th1 proinflammatory response and the inflammatory MRI parameters. The author reviews the data about experimental studies and clinical trials using mesenchymal stem cells for the treatment of multiple sclerosis.

  6. [Common German language nomenclature for systemic sclerosis].

    PubMed

    Aringer, M; Müller-Ladner, U; Burkhardt, H; Distler, J H W; Distler, O; Graninger, W B; Günther, C; Hunzelmann, N; Kiener, H; Sticherling, M; Sunderkötter, C; Walker, U A; Riemekasten, G

    2015-03-01

    Large data bases and the projects arising from them have led to a much improved understanding of systemic sclerosis over the last decade. Serology has developed further so that more autoantibodies are available for routine testing. Capillary microscopy has become standard and relevant progress has also been made in therapy. Many diagnostic terms found in medical documentation do not adequately reflect this progress. The nomenclature is inconsistent and, therefore, confusing. The international classification of diseases (ICD) nomenclature is, from our point of view, also in need of improvement. This article aims to reestablish a common German language standard for systemic sclerosis, which reflects current knowledge and is suitable for implementation in the clinical routine.

  7. Current frontiers in systemic sclerosis pathogenesis.

    PubMed

    Ciechomska, Marzena; van Laar, Jacob; O'Reilly, Steven

    2015-06-01

    Systemic sclerosis is an autoimmune disease characterised by vascular dysfunction, impaired angiogenesis, inflammation and fibrosis. There is no currently accepted disease-modifying treatment with only autologous stem cell transplant showing clinically meaningful benefit. The lack of treatment options reflects our lack of understanding of the precise molecular mechanisms occurring in the disease. Recent investigations have begun to decipher the molecular pathways underpinning the different aspects of the disease and may provide a rational clinical target(s). Uncovering the molecular mechanisms of the disease is important in understanding systemic sclerosis treatment. The aim of this review was to examine the current thinking in SSc pathogenesis and will offer novel areas for research which may yield novel therapeutics.

  8. Teriflunomide in relapsing multiple sclerosis: therapeutic utility.

    PubMed

    Freedman, Mark S

    2013-09-01

    Teriflunomide is an oral, once-daily disease-modifying therapy (DMT) approved in the USA, Australia, and Argentina for the treatment of relapsing forms of multiple sclerosis (RMS). Teriflunomide reversibly limits the expansion of activated T and B cells associated with the inflammatory process purportedly involved in multiple sclerosis pathogenesis, while preserving lymphocytes for routine immune surveillance. In an extensive clinical development program, teriflunomide demonstrated consistent benefits on both clinical and magnetic resonance imaging outcomes. In long-term studies, teriflunomide treatment was associated with low rates of relapse and disability progression for up to 8 years. The safety profile of teriflunomide has been well characterized, with adverse events generally mild to moderate in nature and infrequently leading to permanent treatment discontinuation. The evidence reviewed here indicates that teriflunomide is an effective addition to the current DMTs used to treat RMS. PMID:23997924

  9. Multiple sclerosis--new treatment modalities.

    PubMed

    Totaro, Rocco; Di Carmine, Caterina; Marini, Carmine; Carolei, Antonio

    2015-12-01

    Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference. PMID:26831413

  10. The Diagnostic Challenge of Multiple Sclerosis

    PubMed Central

    Seland, T. Peter

    1984-01-01

    Multiple sclerosis is a common cause of many neurological complaints and disabilities among young, adult Canadians. In the absence of a reliable and specific laboratory test for the disease, the diagnosis is established primarily by clinical criteria, which are outlined in this article. Recent advances in immunology, neurophysiology and neuroimaging have provided techniques to improve diagnostic confidence, particularly in early or atypical cases. PMID:21278960

  11. Gastric Antral Vascular Ectasia in Systemic Sclerosis

    PubMed Central

    Johnson, Jill; Derk, Chris T.

    2011-01-01

    Gastric antral vascular ectasia is a not so well-understood, and more rare, gastrointestinal manifestation of Systemic Sclerosis which can lead to chronic anemia. A high suspicion and better understanding of this rare manifestation is needed for early detection and treatment. Therapeutic regiments include iron supplementation with acid suppressive therapy, while endoscopic intervention has been shown to be successful in most cases, with gastrectomy or antrectomy rarely needed. PMID:22121374

  12. Update on therapeutic options for multiple sclerosis.

    PubMed

    McCoyd, Matthew

    2013-08-01

    Multiple sclerosis (MS) is one of the most common neurologic disorders that affects young people. The disorder has long been associated with clinical relapses and a disabling course. However, there has been a rapid expansion in the available treatment options for MS, and new insights into existing therapies, as decades of research has begun to produce tangible treatment results leading to newly approved an emerging therapies. PMID:23896508

  13. Teriflunomide for the treatment of multiple sclerosis.

    PubMed

    Oh, Jiwon; O'Connor, Paul W

    2013-02-01

    Several novel oral agents are emerging for use in multiple sclerosis (MS). Among these oral agents, teriflunomide is showing promise with respect to clinical efficacy and safety in relapsing MS patients. In this review, the authors clarify the role of teriflunomide in the context of current and emerging MS treatment options by summarizing salient points on the use of teriflunomide in MS, with a discussion of teriflunomide's development, pharmacologic properties, preclinical and clinical trials, and safety and tolerability. PMID:23709212

  14. Eosinophilic Fasciitis: A Rare Skin Sclerosis

    PubMed Central

    Servy, Amandine; Clérici, Thierry; Malines, Caroline; Le Parc, Jean-Marie; Côté, Jean-François

    2011-01-01

    Eosinophilic fasciitis (Schulman's syndrome) is a rare disease with specific clinical symptoms such as the groove sign which facilitate diagnosis. We report a typical case of eosinophilic fasciitis in an otherwise healthy 49-year-old man who presented with “prayer and groove signs”. Histological analysis showed sclerosis and eosinophilic infiltration of the fascia. The patient was successfully treated with systemic corticotherapy and Cyclosporine. A short review of the clinicopathological features of the lesions is presented. PMID:21151540

  15. "Disease modifying nutricals" for multiple sclerosis.

    PubMed

    Schmitz, Katja; Barthelmes, Julia; Stolz, Leonie; Beyer, Susanne; Diehl, Olaf; Tegeder, Irmgard

    2015-04-01

    The association between vitamin D and multiple sclerosis has (re)-opened new interest in nutrition and natural compounds in the prevention and treatment of this neuroinflammatory disease. The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy, sodium chloride and trace elements, and fat soluble vitamins including D, A and E were all considered as disease-modifying nutraceuticals. Studies in experimental autoimmune encephalomyelitis mice suggest that poly-unsaturated fatty acids and their 'inflammation-resolving' metabolites and the gut microflora may reduce auto-aggressive immune cells and reduce progression or risk of relapse, and infection with whipworm eggs may positively change the gut-brain communication. Encouraged by the recent interest in multiple sclerosis-nutrition nature's pharmacy has been searched for novel compounds with anti-inflammatory, immune-modifying and antioxidative properties, the most interesting being the scorpion toxins that inhibit specific potassium channels of T cells and antioxidative compounds including the green tea flavonoid epigallocatechin-3-gallate, curcumin and the mustard oil glycoside from e.g. broccoli and sulforaphane. They mostly also inhibit pro-inflammatory signaling through NF-κB or toll-like receptors and stabilize the blood brain barrier. Disease modifying functions may also complement analgesic and anti-spastic effects of cannabis, its constituents, and of 'endocannabinoid enhancing' drugs or nutricals like inhibitors of fatty acid amide hydrolase. Nutricals will not solve multiple sclerosis therapeutic challenges but possibly support pharmacological interventions or unearth novel structures.

  16. Treatment of pediatric multiple sclerosis and variants.

    PubMed

    Pohl, D; Waubant, E; Banwell, B; Chabas, D; Chitnis, T; Weinstock-Guttman, B; Tenembaum, S

    2007-04-17

    Studies in adult patients with multiple sclerosis (MS) suggest significant benefit of early treatment initiation. However, there are no approved therapies for children and adolescents with MS. For adult MS, tolerability and efficacy of several immunomodulatory and immunosuppressive drugs have been demonstrated. Guidelines for the use of these MS therapies in children do not exist. Several small cohort studies of the safety and tolerability of disease-modifying therapies (DMT) in children and adolescents with MS have been recently reported. The side effects of interferon beta (IFNB) and glatiramer acetate (GA) appear to be similar to those reported by adults. The long-term tolerability and safety have yet to be established and efficacy data have yet to be studied. In view of the potential for significant long-term physical and cognitive disability in children with MS, and recent evidence that initiation of immunomodulatory therapy early in the course of MS improves long-term prognosis, an increasing number of children and adolescents with MS are being offered the DMT approved for adults. This review summarizes current knowledge of DMT in pediatric MS and experience in several centers treating pediatric MS and MS variants such as neuromyelitis optica or Devic disease, Balo concentric sclerosis, Marburg acute MS, and Schilder disease (myelinoclastic diffuse sclerosis). Finally, an overview of symptomatic MS therapies and experiences with these treatments in pediatric patients is provided. PMID:17438239

  17. Genes and Environment in Multiple Sclerosis project: A platform to investigate multiple sclerosis risk.

    PubMed

    Xia, Zongqi; White, Charles C; Owen, Emily K; Von Korff, Alina; Clarkson, Sarah R; McCabe, Cristin A; Cimpean, Maria; Winn, Phoebe A; Hoesing, Ashley; Steele, Sonya U; Cortese, Irene C M; Chitnis, Tanuja; Weiner, Howard L; Reich, Daniel S; Chibnik, Lori B; De Jager, Philip L

    2016-02-01

    The Genes and Environment in Multiple Sclerosis project establishes a platform to investigate the events leading to multiple sclerosis (MS) in at-risk individuals. It has recruited 2,632 first-degree relatives from across the USA. Using an integrated genetic and environmental risk score, we identified subjects with twice the MS risk when compared to the average family member, and we report an initial incidence rate in these subjects that is 30 times greater than that of sporadic MS. We discuss the feasibility of large-scale studies of asymptomatic at-risk subjects that leverage modern tools of subject recruitment to execute collaborative projects.

  18. Pleomorphic xanthoastrocytoma in a case of tuberous sclerosis

    PubMed Central

    Martin, Arvind G.; Singh, Mutum Samarendra; Idris, Badrisyah; Abdullah, Jafri Malin

    2014-01-01

    Tuberous sclerosis is a known phakomatosis and the associated finding of a subependymal giant cell astrocytoma is common with this disorder. A case of tuberous sclerosis with a finding not previously reported, i.e. that of a pleomorphic xanthoastrocytoma, is presented here. PMID:25002765

  19. Multiple sclerosis and human T-cell lymphotropic retroviruses

    NASA Astrophysics Data System (ADS)

    Koprowski, Hilary; Defreitas, Elaine C.; Harper, Mary E.; Sandberg-Wollheim, Magnhild; Sheremata, William A.; Robert-Guroff, Marjorie; Saxinger, Carl W.; Feinberg, Mark B.; Wong-Staal, Flossie; Gallo, Robert C.

    1985-11-01

    A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

  20. Clustering of multiple sclerosis in Galion, Ohio, 1982-1985

    SciTech Connect

    Ingalls, T.H. )

    1989-09-01

    Epidemiologic evidence indicates that the outbreak of 30-40 cases of multiple sclerosis and other demyelinating syndromes in Galion, Ohio, USA, during 1982-1985 was related to an excess concentration of heavy-metal wastes, especially of cadmium and chromium in sewage and river water. Both multiple sclerosis and myasthenia gravis were diagnosed by board-certified neurologists.

  1. Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

    ERIC Educational Resources Information Center

    Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

    2004-01-01

    This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

  2. Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

    ERIC Educational Resources Information Center

    Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

    2009-01-01

    Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

  3. Neuroepileptic Correlates of Autistic Symptomatology in Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Bolton, Patrick F.

    2004-01-01

    Tuberous sclerosis is a genetic condition that is strongly associated with the development of an autism spectrum disorder. However, there is marked variability in expression, and only a subset of children with tuberous sclerosis develop autism spectrum disorder. Clarification of the mechanisms that underlie the association and variability in…

  4. Tuberous Sclerosis Complex: A Roadmap for Future Research.

    PubMed

    Jeong, Anna

    2016-07-01

    Investigators from the NINDS and the Tuberous Sclerosis Alliance sponsored a workshop in March 2015, which joined basic scientists and clinicians with expertise in various aspects of Tuberous Sclerosis Complex (TSC), in order to assess the current state of TSC research and to set future goals. PMID:27617567

  5. [The role of vitamin D in multiple sclerosis].

    PubMed

    Kfoczyńska, Medea; Kucharska, Alicja; Sińska, Beata

    2015-04-08

    Multiple sclerosis is a chronic, inflammatory, demyelinating disease which affects the central nervous system and is linked to autoimmune disorders. Although the precise causes of multiple sclerosis remain unknown, some evidence points towards hypovitaminosis D. Apart from the maintenance of calcium and phosphorus homeostasis, vitamin D also plays a major role in other aspects of human health. It is caused by the vitamin D receptor, which is present in many human organs and tissues. Vitamin D is an immunomodulating factor and accordingly has a potential to be effective in both preventing and treating autoimmune diseases, including multiple sclerosis. The aim of this review was to present up-to-date knowledge about vitamin D, especially its impact on risk of multiple sclerosis onset, relapses, and potential to modify the immune response. A further objective was to describe the role of vitamin D supplementation and its provision in the everyday diet for both prevention and treatment of multiple sclerosis.

  6. [Current aspects of therapy conversion for multiple sclerosis].

    PubMed

    Kolber, P; Luessi, F; Meuth, S G; Klotz, L; Korn, T; Trebst, C; Tackenberg, B; Kieseier, B; Kümpfel, T; Fleischer, V; Tumani, H; Wildemann, B; Lang, M; Flachenecker, P; Meier, U; Brück, W; Limmroth, V; Haghikia, A; Hartung, H-P; Stangel, M; Hohlfeld, R; Hemmer, B; Gold, R; Wiendl, H; Zipp, F

    2015-10-01

    In recent years the approval of new substances has led to a substantial increase in the number of course-modifying immunotherapies available for multiple sclerosis. Therapy conversion therefore represents an increasing challenge. The treatment options sometimes show complex adverse effect profiles and necessitate a long-term and comprehensive monitoring. This article presents an overview of therapy conversion of immunotherapies for multiple sclerosis in accordance with the recommendations of the Disease-Related Competence Network for Multiple Sclerosis and the German Multiple Sclerosis Society as well as the guidelines on diagnostics and therapy for multiple sclerosis of the German Society of Neurology and the latest research results. At the present point in time it should be noted that no studies have been carried out for most of the approaches for therapy conversion given here; however, the recommendations are based on theoretical considerations and therefore correspond to recommendations at the level of expert consensus, which is currently essential for the clinical daily routine.

  7. Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

    PubMed

    Lee, Jason J; Pope, Janet E

    2016-02-01

    Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

  8. High-fat and ketogenic diets in amyotrophic lateral sclerosis.

    PubMed

    Paganoni, Sabrina; Wills, Anne-Marie

    2013-08-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials.

  9. Exercise Training in Progressive Multiple Sclerosis

    PubMed Central

    Paulseth, John E.; Dove, Carin; Jiang, Shucui; Rathbone, Michel P.; Hicks, Audrey L.

    2016-01-01

    Background: There is evidence of the benefits of exercise training in multiple sclerosis (MS); however, few studies have been conducted in individuals with progressive MS and severe mobility impairment. A potential exercise rehabilitation approach is total-body recumbent stepper training (TBRST). We evaluated the safety and participant-reported experience of TBRST in people with progressive MS and compared the efficacy of TBRST with that of body weight–supported treadmill training (BWSTT) on outcomes of function, fatigue, and health-related quality of life (HRQOL). Methods: Twelve participants with progressive MS (Expanded Disability Status Scale scores, 6.0–8.0) were randomized to receive TBRST or BWSTT. Participants completed three weekly sessions (30 minutes) of exercise training for 12 weeks. Primary outcomes included safety assessed as adverse events and patient-reported exercise experience assessed as postexercise response and evaluation of exercise equipment. Secondary outcomes included the Multiple Sclerosis Functional Composite, the Modified Fatigue Impact Scale, and the Multiple Sclerosis Quality of Life–54 questionnaire scores. Assessments were conducted at baseline and after 12 weeks. Results: Safety was confirmed in both exercise groups. Participants reported enjoying both exercise modalities; however, TBRST was reviewed more favorably. Both interventions reduced fatigue and improved HRQOL (P ≤ .05); there were no changes in function. Conclusions: Both TBRST and BWSTT seem to be safe, well tolerated, and enjoyable for participants with progressive MS with severe disability. Both interventions may also be efficacious for reducing fatigue and improving HRQOL. TBRST should be further explored as an exercise rehabilitation tool for patients with progressive MS. PMID:27803637

  10. "Disease modifying nutricals" for multiple sclerosis.

    PubMed

    Schmitz, Katja; Barthelmes, Julia; Stolz, Leonie; Beyer, Susanne; Diehl, Olaf; Tegeder, Irmgard

    2015-04-01

    The association between vitamin D and multiple sclerosis has (re)-opened new interest in nutrition and natural compounds in the prevention and treatment of this neuroinflammatory disease. The dietary amount and type of fat, probiotics and biologicals, salmon proteoglycans, phytoestrogens and protease inhibitor of soy, sodium chloride and trace elements, and fat soluble vitamins including D, A and E were all considered as disease-modifying nutraceuticals. Studies in experimental autoimmune encephalomyelitis mice suggest that poly-unsaturated fatty acids and their 'inflammation-resolving' metabolites and the gut microflora may reduce auto-aggressive immune cells and reduce progression or risk of relapse, and infection with whipworm eggs may positively change the gut-brain communication. Encouraged by the recent interest in multiple sclerosis-nutrition nature's pharmacy has been searched for novel compounds with anti-inflammatory, immune-modifying and antioxidative properties, the most interesting being the scorpion toxins that inhibit specific potassium channels of T cells and antioxidative compounds including the green tea flavonoid epigallocatechin-3-gallate, curcumin and the mustard oil glycoside from e.g. broccoli and sulforaphane. They mostly also inhibit pro-inflammatory signaling through NF-κB or toll-like receptors and stabilize the blood brain barrier. Disease modifying functions may also complement analgesic and anti-spastic effects of cannabis, its constituents, and of 'endocannabinoid enhancing' drugs or nutricals like inhibitors of fatty acid amide hydrolase. Nutricals will not solve multiple sclerosis therapeutic challenges but possibly support pharmacological interventions or unearth novel structures. PMID:25435020

  11. Ultraviolet radiation, vitamin D and multiple sclerosis.

    PubMed

    Lucas, Robyn M; Byrne, Scott N; Correale, Jorge; Ilschner, Susanne; Hart, Prue H

    2015-10-01

    There is compelling epidemiological evidence that the risk of developing multiple sclerosis is increased in association with low levels of sun exposure, possibly because this is associated with low vitamin D status. Recent work highlights both vitamin D and non-vitamin D effects on cellular immunity that suggests that higher levels of sun exposure and/or vitamin D status are beneficial for both MS risk and in ameliorating disease progression. Here we review this recent evidence, focusing on regulatory cells, dendritic cells, and chemokines and cytokines released from the skin following exposure to ultraviolet radiation.

  12. Heterogeneity versus homogeneity of multiple sclerosis

    PubMed Central

    Sato, Fumitaka; Martinez, Nicholas E; Omura, Seiichi; Tsunoda, Ikuo

    2011-01-01

    The 10th International Congress of Neuroimmunology, including the 10th European School of Neuroimmunology Course, was held by the International Society of Neuroimmunology in Sitges (Barcelona, Spain) on 26–30 October 2010. The conference covered a wide spectrum of issues and challenges in both basic science and clinical aspects of neuroimmunology. Data and ideas were shared through a variety of programs, including review talks and poster sessions. One of the topics of the congress was whether multiple sclerosis is a homogenous or heterogenous disease, clinically and pathologically, throughout its course. PMID:21426254

  13. Developing a community multiple sclerosis nursing service.

    PubMed

    Quinn, Debbie; Adams, John

    2014-05-20

    Reforms to the NHS following the passing of the Health and Social Care Act 2012 have created new purchaser organisations with responsibility for planning the configuration of healthcare services in their geographic areas. If a community multiple sclerosis (MS) nursing service is to survive in this environment, it must demonstrate its ability to contribute to achieving the purchaser organisations' objectives. Evaluation data, such as hospital admission avoidance and patient satisfaction, will be crucial in demonstrating the community MS nursing service's clinical and economic effectiveness. A strengths, weaknesses, opportunities and threats (SWOT) analysis of the issues facing a community MS service in this environment is provided. PMID:24823591

  14. Genetics, Epigenetics, and Genomics of Systemic Sclerosis.

    PubMed

    Salazar, Gloria; Mayes, Maureen D

    2015-08-01

    Systemic sclerosis (SSc) is a complex autoimmune disease that occurs in a genetically susceptible host. Genetic studies performed so far reveal that multiple genetic loci contribute to disease susceptibility in SSc. The purpose of this review is to discuss the current knowledge of genetics in SSc by exploring the observational evidence, the different genetic studies, and their modalities as well as the most relevant genes discovered by these. The importance of gene expression variation and the different mechanisms that govern it, including the recently discovered field of epigenetics, are also explored, with an emphasis on microRNA.

  15. Systemic Sclerosis with Multiple Pulmonary Manifestations

    PubMed Central

    Suresh, Parinita; Reddy, Venkata Siva Prasad; Sharma, Tarun; Salim, Nabil Ahmed

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune multisystem disorder characterized by endothelial dysfunction and fibroblast dysfunction, which results in progressive fibrosis of the skin and internal organs more frequently the lungs and gastro intestinal tract. Pulmonary involvement is common in the course of SSc, with Interstitial Lung Disease (ILD) and Pulmonary Arterial Hypertension (PAH) being the leading causes of death. Here we report, case of an elderly female patient presenting with Diffuse SSc with multiple uncommon pulmonary manifestations like ILD with Usual Interstitial Pneumonia (UIP) pattern (usually less common), PAH and right sided pleural effusion. PMID:27504339

  16. Monthly distribution of multiple sclerosis patients' births

    NASA Astrophysics Data System (ADS)

    Bharanidharan, Padmanabhan

    As part of an integrated geographical and environmental epidemiological study of multiple sclerosis (MS) in Budapest's Pesterzsébet district, many biometeorological variables were specifically examined. Also, the monthly distribution of birthdates of MS patients resident in the district was plotted. Patients reliably diagnosed with MS were found to have been born in greater numbers in the months of April and October, precisely 6 months apart. This finding indicates the presence of natural non-genetic factors in the creation of MS susceptibility, affecting the nervous system at the crucial time of myelination.

  17. Proton Magnetic Resonance Spectroscopy in Multiple Sclerosis

    PubMed Central

    Sajja, Balasrinivasa R.; Wolinsky, Jerry S.

    2008-01-01

    Synopsis Proton magnetic resonance spectroscopy (1H-MRS) provides tissue metabolic information in vivo. This article reviews the role of MRS-determined metabolic alterations in lesions, normal appearing white matter, gray matter, and spinal cord in advancing our knowledge of pathological changes in multiple sclerosis (MS). In addition, the role of MRS in objectively evaluating therapeutic efficacy is reviewed. This potential metabolic information makes MRS a unique tool to follow MS disease evolution, understanding its pathogenesis, evaluating the disease severity, establishing a prognosis, and objectively evaluating the efficacy of therapeutic interventions. PMID:19064199

  18. [Update on Current Care Guideline: Multiple sclerosis].

    PubMed

    Remes, Anne; Airas, Laura; Atula, Sari; Färkkilä, Markus; Hartikainen, Päivi; Koivisto, Keijo; Mäenpää, Eliisa; Ruutiainen, Juhani; Sumelahti, Marja-Liisa

    2015-01-01

    Treatment for relapsing-remitting multiple sclerosis (RRMS) is initiated upon fulfillment of new McDonald 2010 criteria for RRMS. In addition, lumbar puncture is an essential diagnostic method. Interferon-β, dimethyl fumarate, glatiramer acetate and teriflunomide are the first-line immunomodulating drugs (IMD) for RRMS. If the disease is active according to clinical or MRI evaluation during the first-line IMD treatment, alemtuzumab, fingolimod or natalizumab may be considered as second-line therapies. IMD treatment is discontinued upon the transition of RRMS to secondary progressive phase. Rehabilitation should be considered at every phase of the disease. PMID:26237913

  19. [Prevention of multiple sclerosis: a realistic goal?].

    PubMed

    Vukusic, S

    2012-11-01

    Multiple sclerosis (MS) is the most frequent source of chronic neurological disability in Western countries, and its incidence and prevalence are increasing. However, it is possible to determine its prodromal phase and the radiological, biological and immunological endophenotypes that are present before the clinical onset of the disease, despite remaining unseen with the naked eye. In this context, greater knowledge of the aetiological factors, both genetic and environmental, may lead the way towards primary prevention strategies for MS in the near future. PMID:22989784

  20. Refractory anemia in systemic sclerosis: myelodisplastic syndrome

    PubMed Central

    Sargın, Gökhan; Şentürk, Taşkın; Yavaşoğlu, İrfan

    2015-01-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by small vessel vasculopathy, autoantibodies, and skin or visceral organ fibrosis (lung, oesophagus, kidney etc.) as a result of extracellular collagen deposition. The cancer risk is higher in many rheumatic diseases, including SSc. Various defined malignancies may develop in 3%–11% of patients with SSc. These solid tumors are generally observed in the lung, oesophagus, or breast. In addition, an increased risk for hematological cancers were reported in literature. Herein, we describe an interesting case of SSc complicated by myelodisplastic syndrome (MDS). Our aim is to draw attention to developing cancers and the rare occurence of MDS in patients with SSc.

  1. Symptom management in patients with multiple sclerosis.

    PubMed

    Ziemssen, Tjalf

    2011-12-01

    Multiple sclerosis is a complex disease associated with a wide variety of different symptoms that can affect the ability of multiple sclerosis patients to carry out normal activities of daily living. Although a myriad of symptoms can afflict these patients, the most commonly reported include fatigue, mood disorders, changes in cognitive function or memory, sensory changes (numbness, pain, vibrations), motor changes (loss of balance, poor coordination, muscle weakness or stiffness), vision changes (double vision, blurred vision, loss of vision) and bladder or bowel dysfunction. Treatments are available that can help minimise some of these symptoms and relieve patient distress. After the diagnosis has been established and a decision taken regarding initiation of immunomodulatory treatments, the majority of management decisions with which the physician will be confronted will concern symptom management. Whereas some symptoms are relatively easily treated, others are more difficult to manage. Management involves rehabilitation, pharmacological treatments and surgical procedures. Successful symptom management is a key determinant of quality of life for the patient and is the basis for improving physical and psychological function.

  2. Semantic deficits in amyotrophic lateral sclerosis.

    PubMed

    Leslie, Felicity V C; Hsieh, Sharpley; Caga, Jashelle; Savage, Sharon A; Mioshi, Eneida; Hornberger, Michael; Kiernan, Matthew C; Hodges, John R; Burrell, James R

    2015-03-01

    Our objective was to investigate, and establish neuroanatomical correlates of, semantic deficits in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD), compared to semantic dementia (SD) and controls. Semantic deficits were evaluated using a naming and semantic knowledge composite score, comprising verbal and non-verbal neuropsychological measures of single-word processing (confrontational naming, comprehension, and semantic association) from the Sydney Language Battery (SYDBAT) and Addenbrooke's Cognitive Examination - Revised (ACE-R). Voxel based morphometry (VBM) analysis was conducted using the region of interest approach. In total, 84 participants were recruited from a multidisciplinary research clinic in Sydney. Participants included 17 patients with ALS, 19 with ALS-FTD, 22 with SD and 26 age- and education-matched healthy controls. Significant semantic deficits were observed in ALS and ALS-FTD compared to controls. The severity of semantic deficits varied across the clinical phenotypes: ALS patients were less impaired than ALS-FTD patients, who in turn were not as impaired as SD patients. Anterior temporal lobe atrophy significantly correlated with semantic deficits. In conclusion, semantic impairment is a feature of ALS and ALS-FTD, and reflects the severity of temporal lobe pathology.

  3. Amyotrophic lateral sclerosis: one or multiple causes?

    PubMed Central

    Bastos, Aline Furtado; Orsini, Marco; Machado, Dionis; Mello, Mariana Pimentel; Nader, Sergio; Silva, Júlio Guilherme; da Silva Catharino, Antonio M.; de Freitas, Marcos R.G.; Pereira, Alessandra; Pessoa, Luciane Lacerda; Sztajnbok, Flavio R.; Leite, Marco Araújo; Nascimento, Osvaldo J.M.; Bastos, Victor Hugo

    2011-01-01

    The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients. PMID:21785676

  4. Dermatoglyphic features in patients with multiple sclerosis

    PubMed Central

    Sabanciogullari, Vedat; Cevik, Seyda; Karacan, Kezban; Bolayir, Ertugrul; Cimen, Mehmet

    2014-01-01

    Objective: To examine dermatoglyphic features to clarify implicated genetic predisposition in the etiology of multiple sclerosis (MS). Methods: The study was conducted between January and December 2013 in the Departments of Anatomy, and Neurology, Cumhuriyet University School of Medicine, Sivas, Turkey. The dermatoglyphic data of 61 patients, and a control group consisting of 62 healthy adults obtained with a digital scanner were transferred to a computer environment. The ImageJ program was used, and atd, dat, adt angles, a-b ridge count, sample types of all fingers, and ridge counts were calculated. Results: In both hands of the patients with MS, the a-b ridge count and ridge counts in all fingers increased, and the differences in these values were statistically significant. There was also a statistically significant increase in the dat angle in both hands of the MS patients. On the contrary, there was no statistically significant difference between the groups in terms of dermal ridge samples, and the most frequent sample in both groups was the ulnar loop. Conclusions: Aberrations in the distribution of dermatoglyphic samples support the genetic predisposition in MS etiology. Multiple sclerosis susceptible individuals may be determined by analyzing dermatoglyphic samples. PMID:25274586

  5. Amyotrophic lateral sclerosis disease progression model.

    PubMed

    Gomeni, Roberto; Fava, Maurizio

    2014-03-01

    Our objective was to develop: 1) a longitudinal model to describe amyotrophic lateral sclerosis (ALS) disease progression using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R); and 2) a probabilistic model to estimate the presence of clusters of trajectories in ALS progression over 12 months of treatment. Three hundred and thirty-eight patients treated with placebo from the PRO-ACT database were included in the analyses. A non-linear Weibull model best described the ALS disease progression, and a stepwise logistic regression approach was used to select the variables predicting a slow or fast disease progression. Results identified two clusters of trajectories: 1) slow disease progressors (46% of patients with a change from baseline of 13%); 2) fast disease progressors (54% of patients with a change from baseline of 49%). ROC curve analysis estimated the optimal cut-off for classifying patients as slow or fast disease progressors given ALSFRS-R measurements at 2-4 weeks. Results showed that the degree of ALS disease progression quantified by the ALSFRS-R symptomatic change on placebo is highly heterogeneous. In conclusion, this finding indicates the potential interest of disease progression models for implementing a population enrichment strategy to control the level of heterogeneity in the patients included in new trials.

  6. Tuberous sclerosis complex presenting as bilateral large renal angiomyolipomas.

    PubMed

    Redkar, Neelam; Patil, Meenakshi Amit; Dhakate, Tushar; Kolhe, Prasad

    2012-01-01

    Tuberous sclerosis is an inherited disorder that can present with seizures, mental retardation, cutaneous lesions and visceral hamartomas, but can be entirely asymptomatic. The disease occurs in 1:100 000 persons in all races with nearly equal distribution between the sexes. Tuberous sclerosis is often associated with renal angiomyolipomas (AMLs), which occur in up to 80% of these patients. Here we report a case of a patient who presented with bilateral large renal AMLs and was detected to have tuberous sclerosis complex. PMID:22878994

  7. Animal models of systemic sclerosis: their utility and limitations

    PubMed Central

    Artlett, Carol M

    2014-01-01

    Without doubt, animal models have provided significant insights into our understanding of the rheumatological diseases; however, no model has accurately replicated all aspects of any autoimmune disease. Recent years have seen a plethora of knockouts and transgenics that have contributed to our knowledge of the initiating events of systemic sclerosis, an autoimmune disease. In this review, the focus is on models of systemic sclerosis and how they have progressed our understanding of fibrosis and vasculopathy, and whether they are relevant to the pathogenesis of systemic sclerosis.

  8. [Update on diagnosis and treatment of multiple sclerosis].

    PubMed

    Depaz, R; Aboab, J; Gout, O

    2013-10-01

    Recent advances in neuroimaging have simplified the diagnostic criteria of multiple sclerosis. Indeed, the diagnosis of multiple sclerosis could be obtained during the first bout of disease flare, very early in the disease course. This is particularly important to shorten the diagnostic delay as early treatment may limit the occurrence of late irreversible disabilities. At the same time, major therapeutic advances have been obtained and new drugs that are well tolerated and more effective, despite the possible rare but potentially severe side effects are been developed. This article reviews the modern diagnostic and therapeutic strategies in multiple sclerosis in accordance with the recent obtained advances.

  9. ONION PEEL APPEARANCE IN BALOS CONCENTRIC SCLEROSIS--A VARIANT OF MULTIPLE SCLEROSIS.

    PubMed

    Arif, Saeed; Wali, Muhammad Waseem; Slehria, Atiq Ur Rehman; Khalid, Hina; Malik, Hamza

    2015-01-01

    Balo's concentric sclerosis (BCS) is a variant of multiple sclerosis (MS). It may present as a lesior clinically and radiologically indistinguishable from brain tumour particularly on computerized tomography (CT) scans. Diagnosis only gets clear when magnetic resonance imaging and spectroscopy (MRI & MRS) and brain biopsy is done. We report a case of 30 year old male with progressive headache and left hemi paresis for 3 weeks. There was upper motor neuron (UMN) facial palsy on the left with bilateral papilledema. CT scan of brain showed large hypo-dense area in right frontoparietal lobe consistent with brain tumour. On MRI the diagnosis of BCS was made on basis of concentric lesions of myelinated and demyelinated rings. Demyelination wa confirmed on brain biopsy. PMID:26182786

  10. Automatic memory processes in patients with multiple sclerosis.

    PubMed

    Grafman, J; Rao, S; Bernardin, L; Leo, G J

    1991-10-01

    To better understand the nature of the memory deficit in patients with multiple sclerosis, we designed a study to compare automatic vs effortful memory processes. Forty-one patients with definite multiple sclerosis and 45 demographically matched normal control subjects were administered two tasks designed to assess both automatic (monitoring frequency and modality) and effortful (free and cued-recall) processing. Results indicated that patients with multiple sclerosis, as expected, were significantly impaired on memory measures requiring effort, but performed normally on automatic measures. Performance on the memory indexes did not correlate with self-reported depression. The implications of these findings for delineating the locus of the memory impairment in multiple sclerosis is discussed. PMID:1929900

  11. Multiple sclerosis in the Cambridge health district of east Anglia.

    PubMed Central

    Mumford, C J; Fraser, M B; Wood, N W; Compston, D A

    1992-01-01

    A survey of multiple sclerosis (MS) in the Cambridge Health District has identified 374 cases in a population of 288,410, giving a prevalence of 130 per 100,000. A total of 322 cases (86%) had either clinically definite or probable multiple sclerosis on 1 July 1990 (112 per 100,000) and 52 cases (14%) had suspected multiple sclerosis (18 per 100,000.) The incidence during 1989-91 was 5.94 per 100,000 per year. The prevalence figure is higher than in recent surveys from other southern parts of the United Kingdom, but correction for the age and sex characteristics of the at risk population eliminates these differences. The overall prevalence of multiple sclerosis is probably between 108 and 120 per 100,000 in the southern United Kingdom. PMID:1431950

  12. Postsecondary Education for Individuals with Multiple Sclerosis: Issues and Strategies.

    ERIC Educational Resources Information Center

    Yagodich, Nancy L.; Wolfe, Pamela S.; Boone, Rosalie S.

    2000-01-01

    Describes characteristics of multiple sclerosis and the implications of its manifestations for postsecondary education. Provides a checklist for students selecting a postsecondary institution regarding general considerations, academic accommodations, support and services, and self-assessment. (SK)

  13. Jaw, blink and corneal reflex latencies in multiple sclerosis.

    PubMed Central

    Sanders, E A; Ongerboer de Visser, B W; Barendswaard, E C; Arts, R J

    1985-01-01

    Jaw, blink and corneal reflexes, which all involve the trigeminal system, were recorded in 54 patients with multiple sclerosis; thirty-seven of these patients were classified as having definite multiple sclerosis and 17 as indefinite multiple sclerosis, according to Schumacher's criteria. The jaw reflex was abnormal less frequently than either of the other two reflexes, but in four cases it was the only abnormal reflex found. Testing a combination of two or three trigeminal reflexes did not yield a higher incidence of abnormalities than testing the blink or corneal reflex alone. Nine patients showed abnormal reflexes which were unexpected on the basis of clinical symptoms. The combined recordings demonstrate at least one abnormal reflex in 74% of the patients. The various types of reflex abnormalities reflect major damage to different parts of the trigeminal system and may therefore make an important contribution to the diagnosis of multiple sclerosis. PMID:4087004

  14. Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses.

    PubMed

    Farez, Mauricio F; Mascanfroni, Ivan D; Méndez-Huergo, Santiago P; Yeste, Ada; Murugaiyan, Gopal; Garo, Lucien P; Balbuena Aguirre, María E; Patel, Bonny; Ysrraelit, María C; Zhu, Chen; Kuchroo, Vijay K; Rabinovich, Gabriel A; Quintana, Francisco J; Correale, Jorge

    2015-09-10

    Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis. PMID:26359987

  15. Autism Phenotypes in Tuberous Sclerosis Complex: Diagnostic and Treatment Considerations.

    PubMed

    Gipson, Tanjala T; Poretti, Andrea; Thomas, Emily A; Jenkins, Kosunique T; Desai, Sonal; Johnston, Michael V

    2015-12-01

    Tuberous sclerosis complex is a multisystem, chronic genetic condition characterized by systemic growth of benign tumors and often accompanied by epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless, the neurodevelopmental phenotype of these patients is not often detailed. The authors describe 3 individuals with tuberous sclerosis complex who share common characteristics that can help to identify a distinct profile of autism spectrum disorder. These findings include typical cognitive development, expressive and pragmatic language deficits, and anxiety. The authors also describe features specific to tuberous sclerosis complex that require consideration before diagnosing an autism spectrum disorder. Identifying distinct profiles of autism spectrum disorder in tuberous sclerosis complex can help optimize treatment across the life span. PMID:26303410

  16. Amyotrophic lateral sclerosis: early contributions of Jean-Martin Charcot.

    PubMed

    Goetz, C G

    2000-03-01

    Amyotrophic lateral sclerosis is historically an important entity because its manifestations involve distinct signs that can be correlated with gray and white matter lesions at specific sites within the central nervous system. Working at the end of the nineteenth century, the celebrated neurologist, Jean-Martin Charcot, used this disorder as a prototypic example of the power of his research method, termed "méthode anatomoclinique." Using clinical cases and autopsy material, he showed how anatomical lesions in the nervous system could be accurately determined by the presence of carefully analyzed clinical signs. Charcot's work on amyotrophic lateral sclerosis brought together neurological entities formerly considered as disparate disorders, primary amyotrophy and primary lateral sclerosis. In addition, these studies contributed to the understanding of spinal cord and brain stem anatomy and the organization of the normal nervous system. Because of Charcot's fundamental contributions, the eponym "Charcot's disease" has been used internationally in association with amyotrophic lateral sclerosis.

  17. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    PubMed

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  18. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.

    PubMed Central

    Pandey, J P; Goust, J M; Salier, J P; Fudenberg, H H

    1981-01-01

    Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype. PMID:6787085

  19. Immunoglobulin G heavy chain (Gm) allotypes in multiple sclerosis.

    PubMed

    Pandey, J P; Goust, J M; Salier, J P; Fudenberg, H H

    1981-06-01

    Serum samples from 70 Caucasian patients with multiple sclerosis were typed for nine Gm markers. Significant association was found with the Gm 1,17;21 phenotype, and the relative risk for individuals with this phenotype was calculated at 3.6. The data indicate that Caucasians positive for Gm 1,17;21 are almost four times more likely to develop multiple sclerosis than those without this phenotype. PMID:6787085

  20. Sero-Negative Systemic Sclerosis: A Rare Presentation

    PubMed Central

    Chander, Rakesh; Singh, Santokh; Charan, Shiv; Gupta, Abhishek

    2016-01-01

    Systemic Sclerosis is a multisystem disease associated with progressive fibrosis of skin and internal organs. It is diagnosed by presence of characteristic clinical findings and is supported by specific serologic abnormalities. ANA is positive in case of systemic sclerosis in 90 percent of cases. We report a rare case of this rare disease where patient was ANA, Antitopoisomerase I (anti-Scl-70), Anticenteromere antibody negative. PMID:27504337

  1. Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.

    PubMed

    Huang, Jeffrey K; Fancy, Stephen P J; Zhao, Chao; Rowitch, David H; Ffrench-Constant, Charles; Franklin, Robin J M

    2011-10-01

    Regeneration of myelin sheaths (remyelination) after central nervous system demyelination is important to restore saltatory conduction and to prevent axonal loss. In multiple sclerosis, the insufficiency of remyelination leads to the irreversible degeneration of axons and correlated clinical decline. Therefore, a regenerative strategy to encourage remyelination may protect axons and improve symptoms in multiple sclerosis. We highlight recent studies on factors that influence endogenous remyelination and potential promising pharmacological targets that may be considered for enhancing central nervous system remyelination.

  2. Neurobehavioral burden of multiple sclerosis with nanotheranostics

    PubMed Central

    Sriramoju, Bhasker; Kanwar, Rupinder K; Kanwar, Jagat R

    2015-01-01

    Multiple sclerosis (MS) is a chronic demyelinating neurological disorder affecting people worldwide; women are affected more than men. MS results in serious neurological deficits along with behavioral compromise, the mechanisms of which still remain unclear. Behavioral disturbances such as depression, anxiety, cognitive impairment, psychosis, euphoria, sleep disturbances, and fatigue affect the quality of life in MS patients. Among these, depression and psychosis are more common than any other neurological disorders. In addition, depression is associated with other comorbidities. Although anxiety is often misdiagnosed in MS patients, it can induce suicidal ideation if it coexists with depression. An interrelation between sleep abnormalities and fatigue is also reported among MS patients. In addition, therapeutics for MS is always a challenge because of the presence of the blood–brain barrier, adding to the lack of detailed understanding of the disease pathology. In this review, we tried to summarize various behavioral pathologies and their association with MS, followed by its conventional treatment and nanotheranostics. PMID:26508863

  3. Hyperimmune goat serum for amyotrophic lateral sclerosis.

    PubMed

    Mackenzie, R; Kiernan, M; McKenzie, D; Youl, B D

    2006-12-01

    The authors report a patient with amyotrophic lateral sclerosis (ALS) who showed a lessening of deterioration in respiratory muscle strength during treatment with hyperimmune goat serum (HGS) (Aimspro). Respiratory function tests (RFTs) were measured by established protocols, and all measurements were expressed as a percentage of normal predicted values. The rate of decline was calculated by linear regression analysis. Respiratory muscle strength decline was less during 13 months of treatment with HGS (mean 1.3% per month, range 0.8-1.7%) compared to the preceding 13 months (mean 2.3% per month, range 1.2-3.1%), while a greater decline would be expected with disease progression. Comparison with similarly affected patients in the literature suggest that a decline of 4-5% per month of predicted values may be expected during the treatment phase.

  4. Autoantibodies as predictive tools in systemic sclerosis.

    PubMed

    Nihtyanova, Svetlana I; Denton, Christopher P

    2010-02-01

    The pathogenetic role of autoantibodies in systemic sclerosis (SSc) remains unclear, but these autoantibodies have been established as strong predictors of disease outcome and the pattern of organ complications in patients with this condition. The three most frequently observed types of SSc-specific autoantibody-anti-centromere antibodies, anti-topoisomerase antibodies and anti-RNA polymerase III antibodies-are found in over 50% of patients; the presence of each is generally exclusive of the others. Although a lot less frequently observed, antibodies directed against U3RNP and Th/To are also specific for scleroderma, whereas anti-Pm/Scl, anti-Ku and anti-U1RNP antibodies are seen mainly in patients with overlap syndromes. Up to 11% of patients with SSc can test negative for antinuclear antibodies. Strong links exist between autoantibody specificities and disease presentation and outcome, which make autoantibodies essential assessment tools in patients with SSc.

  5. Autoantibodies in Systemic Sclerosis: Unanswered Questions

    PubMed Central

    Kayser, Cristiane; Fritzler, Marvin J.

    2015-01-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular abnormalities, and cutaneous and visceral fibrosis. Serum autoantibodies directed to multiple intracellular antigens are present in more than 95% of patients and are considered a hallmark of SSc. They are helpful biomarkers for the early diagnosis of SSc and are associated with distinctive clinical manifestations. With the advent of more sensitive, multiplexed immunoassays, new and old questions about the relevance of autoantibodies in SSc are emerging. In this review, we discuss the clinical relevance of autoantibodies in SSc emphasizing the more recently published data. Moreover, we will summarize recent advances regarding the stability of SSc autoantibodies over the course of disease, whether they are mutually exclusive and their potential roles in the disease pathogenesis. PMID:25926833

  6. Dual diagnosis: rheumatoid arthritis and multiple sclerosis.

    PubMed

    Ozsahin, Mustafa; Dikici, Suber; Kocaman, Gülsen; Besir, Fahri Halit; Baltaci, Davut; Ataoglu, Safinaz

    2014-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common rheumatologic disease in children. Moreover, multiple sclerosis (MS) is the most frequent demyelinating disease and has been associated with various chronic inflammatory diseases. However, its association with JRA has not been frequently described. Autoimmunity in both JRA and MS has been documented in the scientific literature, although there has been no definitive finding that patients with JRA are prone to the development of MS. An increasing frequency of MS resulting from an increased use of antitumor necrosis factor agents in the treatment of rheumatoid arthritis and other chronic inflammatory diseases has been reported recently. In this study, we report on the development of MS in a patient with JRA who did not have a history of antitumor necrosis factor use.

  7. Multiple sclerosis in India: An overview

    PubMed Central

    Singhal, Bhim S.; Advani, Hemali

    2015-01-01

    Multiple sclerosis (MS) is being increasingly diagnosed in India mainly due to increase in the number of practicing neurologists and easy and affordable availability of magnetic resonance imaging (MRI). The clinical features and course are largely similar to those seen in the West. The term optico-spinal MS (Asian MS) was coined in the pre-MRI days. Many such patients turn out to be cases of neuromyelitis optica — a distinct disorder and not a variant of MS. Others have shown the classical features of MS on MRI scan. Several of the disease-modifying agents, not all, are now available in India. Their use, however, has been limited in view of the high cost. PMID:26538844

  8. Innovative Monoclonal Antibody Therapies in Multiple Sclerosis

    PubMed Central

    Kieseier, Bernd C.

    2008-01-01

    The recent years have witnessed great efforts in establishing new therapeutic options for multiple sclerosis (MS), especially for relapsing–remitting disease courses. In particular, the application of monoclonal antibodies provide innovative approaches allowing for blocking or depleting specific molecular targets, which are of interest in the pathogenesis of MS. While natalizumab received approval by the US Food and Drug Administration and the European Medicines Agency in 2006 as the first monoclonal antibody in MS therapy, rituximab, alemtuzumab, and daclizumab were successfully tested for relapsing-remitting MS in small cohorts in the meantime. Here, we review the data available from these recent phase II trials and at the same time critically discuss possible pitfalls which may be relevant for clinical practice. The results of these studies may not only broaden our therapeutic options in the near future, but also provide new insights into disease pathogenesis. PMID:21180564

  9. Electrodiagnosis in persons with amyotrophic lateral sclerosis.

    PubMed

    Joyce, Nanette C; Carter, Gregory T

    2013-05-01

    Electrophysiology remains an important tool in the evaluation of patients presenting with signs and symptoms of motor neuron disease. The electrodiagnostic study should include peripheral nerve conduction studies and needle electromyography to both exclude treatable disease and gather evidence regarding a diagnosis of amyotrophic lateral sclerosis (ALS). The recent changes in the revised El Escorial criteria, recommended by the Awaji-shima consensus group, have increased the diagnostic significance of fasciculation potentials to equal that of fibrillation and positive sharp-wave potentials in the needle electromyography examination of patients suspected of having ALS. In addition, electrophysiologic evidence is now considered equivalent to clinical signs and symptoms in reaching a diagnostic certainty of ALS. These changes, strategies for the design, and implementation of an effective electrodiagnostic evaluation, in addition to electrophysiologic techniques and their relationship to the evaluation of a patient with ALS, are reviewed and discussed.

  10. [Treatment of multiple sclerosis symptoms and exacerbations].

    PubMed

    Prieto González, José María

    2014-12-01

    In the last few years, there has been an explosion of new drugs acting on the clinical course of multiple sclerosis (MS) but less attention has been paid to better knowledge of the symptoms of this disease and their pathogenesis and treatment, which is essential to improve patients' quality of life. Because many patients have numerous concurrent symptoms during their clinical course, their management is complex and consequently it is important to know which symptoms are a direct result of the degenerative lesions of MS. The present article describes all the therapeutic options available for spasticity and its associated pain, paroxystic symptoms, fatigue, genitourinary disorders and sexual dysfunction, tremor, ataxia, gait disorder and cognitive impairment, with special emphasis on novel treatments. The article also defines exacerbations, how to recognize them and the available treatments, mainly oral administration of high-dose methylprednisolone and plasmapheresis. PMID:25732949

  11. Optic neuritis progressing to multiple sclerosis.

    PubMed

    Corona-Vazquez, T; Ruiz-Sandoval, J; Arriada-Mendicoa, N

    1997-02-01

    We report a partially retrospective and longitudinal study of patients with optic neuritis (ON) that developed multiple sclerosis (MS). We assessed clinical features or factors that might differentiate these patients from those with ON that did not develop MS. Of the cases followed, 110 (67%) were found to have an idiopathic origin of the disease; whereas 55 (33%) were found to develop it secondary to another disease. Of the 110 idiopathic cases, 13 (12%), developed MS over an average of 2 years. The results of these patients in the laboratory analyses of blood and CSF as well as the results of the MRI and evoked potential studies, were significantly different from the ON patients without MS. We conclude that the percentage of patients with ON in our sample that developed MS is similar to that found in Japan and is relatively low in comparison to other reports.

  12. Multiple sclerosis in Caucasians and Latino Americans.

    PubMed

    Aguirre-Cruz, Lucinda; Flores-Rivera, José; De La Cruz-Aguilera, Dora Luz; Rangel-López, Edgar; Corona, Teresa

    2011-11-01

    Epidemiological and genetic studies suggest that the prevalence, median age of onset, and specific phenotypes of multiple sclerosis (MS) are different in Caucasians and Latino Americans. Recent epidemiological studies indicate an increase in MS prevalence in Latin America (LA), where the south-north gradient of latitude described for Nordic countries does not exist. Analysis of MS epidemiological and specific aspects in LA suggests that susceptibility and clinical behavior of the disease are related to mixtures and admixtures of genes in the population. MS is not present in Amerindians with Mongoloid genes, such as occurs in other pure ethnic groups. Surely, future studies will be carried out to obtain more reliable information. In this review, we contrast and analyze the available data of MS in LA and endemic countries.

  13. Proton magnetic resonance spectroscopy in multiple sclerosis

    SciTech Connect

    Wolinsky, J.S.; Narayana, P.A.; Fenstermacher, M.J. )

    1990-11-01

    Regional in vivo proton magnetic resonance spectroscopy provides quantitative data on selected chemical constituents of brain. We imaged 16 volunteers with clinically definite multiple sclerosis on a 1.5 tesla magnetic resonance scanner to define plaque-containing volumes of interest, and obtained localized water-suppressed proton spectra using a stimulated echo sequence. Twenty-five of 40 plaque-containing regions provided spectra of adequate quality. Of these, 8 spectra from 6 subjects were consistent with the presence of cholesterol or fatty acids; the remainder were similar to those obtained from white matter of normal volunteers. This early experience with regional proton spectroscopy suggests that individual plaques are distinct. These differences likely reflect dynamic stages of the evolution of the demyelinative process not previously accessible to in vivo investigation.

  14. Astrocytes in the tempest of multiple sclerosis.

    PubMed

    Miljković, Djordje; Timotijević, Gordana; Mostarica Stojković, Marija

    2011-12-01

    Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity-related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes. PMID:21443873

  15. Multiple sclerosis in an adrenoleukodystrophy carrier

    PubMed Central

    Jenkins, Thomas; Sarasamma, Priya; Gillett, Godfrey; Coley, Stuart; Sharrack, Basil

    2011-01-01

    X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disorder, in which accumulation of very long chain fatty acids (VLCFAs) results in damage to the central nervous system. As the disease is X-linked, males are affected severely, but female carriers may also present with neurological symptoms. We report the case of a young adult female, who presented with episodic sensorimotor symptoms. Although she was a heterozygous female carrier of X-ALD, subsequent investigations confirmed a diagnosis of multiple sclerosis (MS). To the best of our knowledge, this is the first reported case of a female X-ALD carrier in which the clinical features were more consistent with co-existent MS than ALD-related pathology. The case serves as a reminder that alternative, more common diagnoses should also be considered in carriers of rare neurological syndromes. PMID:24765366

  16. The unfolded protein response in multiple sclerosis

    PubMed Central

    Stone, Sarrabeth; Lin, Wensheng

    2015-01-01

    The unfolded protein response (UPR) occurs in response to endoplasmic reticulum (ER) stress caused by the accumulation of unfolded or misfolded proteins in the ER. The UPR is comprised of three signaling pathways that promote cytoprotective functions to correct ER stress; however, if ER stress cannot be resolved the UPR results in apoptosis of affected cells. The UPR is an important feature of various human diseases, including multiple sclerosis (MS). Recent studies have shown several components of the UPR are upregulated in the multiple cell types in MS lesions, including oligodendrocytes, T cells, microglia/macrophages, and astrocytes. Data from animal model studies, particularly studies of experimental autoimmune encephalomyelitis (EAE) and the cuprizone model, imply an important role of the UPR activation in oligodendrocytes in the development of MS. In this review we will cover current literature on the UPR and the evidence for its role in the development of MS. PMID:26283904

  17. Polymorphonuclear neutrophil function in systemic sclerosis.

    PubMed Central

    Czirják, L; Dankó, K; Sipka, S; Zeher, M; Szegedi, G

    1987-01-01

    In vitro functions of polymorphonuclear (PMN) neutrophils were studied in 20 patients with progressive systemic sclerosis (PSS). An increase in the basal chemiluminescence (CL) activity of peripheral blood PMNs was found, suggesting that these cells had been preactivated in vivo. Patients with more extensive skin disease or signs of disease progression tended to have higher basal CL values. Active oxygen products during the respiratory burst may increase the extent of inflammatory and fibrotic processes and could be involved in the endothelial injury in PSS. The stimulatory capacity of CL response was normal in our study. No alterations were found in the opsonised yeast phagocytic activity of granulocytes when compared with control values. The binding of erythrocyte-antibody particles was found also to be normal. A depressed chemotactic activity of PMN cells against zymosan activated serum was also shown. The cause of the decreased chemotaxis of PMNs remains to be elucidated. PMID:3592786

  18. [Cannabinoids for symptomatic therapy of multiple sclerosis].

    PubMed

    Husseini, L; Leussink, V I; Warnke, C; Hartung, H-P; Kieseier, B C

    2012-06-01

    Spasticity represents a common troublesome symptom in patients with multiple sclerosis (MS). Treatment of spasticity remains difficult, which has prompted some patients to self-medicate with and perceive benefits from cannabis. Advances in the understanding of cannabinoid biology support these anecdotal observations. Various clinical reports as well as randomized, double-blind, placebo-controlled studies have now demonstrated clinical efficacy of cannabinoids for the treatment of spasticity in MS patients. Sativex is a 1:1 mix of delta-9-tetrahydocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, which recently received a label for treating MS-related spasticity in Germany. The present article reviews the current understanding of cannabinoid biology and the value of cannabinoids as a symptomatic treatment option in MS. PMID:22080198

  19. Motoneuron firing in amyotrophic lateral sclerosis (ALS)

    PubMed Central

    de Carvalho, Mamede; Eisen, Andrew; Krieger, Charles; Swash, Michael

    2014-01-01

    Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal, and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials. PMID:25294995

  20. A comprehensive review of amyotrophic lateral sclerosis

    PubMed Central

    Zarei, Sara; Carr, Karen; Reiley, Luz; Diaz, Kelvin; Guerra, Orleiquis; Altamirano, Pablo Fernandez; Pagani, Wilfredo; Lodin, Daud; Orozco, Gloria; Chinea, Angel

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease affecting motor neurons with an incidence of about 1/100,000. Most ALS cases are sporadic, but 5–10% of the cases are familial ALS. Both sporadic and familial ALS (FALS) are associated with degeneration of cortical and spinal motor neurons. The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, genetic factors, symptoms, diagnostic, treatment, and even the available supplement and management of ALS. This will provide the reader with an advantage of receiving a broad range of information about the disease. PMID:26629397

  1. Rehabilitation of multiple sclerosis patients in India

    PubMed Central

    Surya, Nirmal

    2015-01-01

    Multiple sclerosis (MS) is a chronic progressive disease which is one of the leading causes of handicap in young subjects. The large range of symptoms associated with MS lead to continuing decline in neurologic status and quality of life. The coexistence of physical and cognitive impairments, together with the imprevisible evolution of the disease makes MS rehabilitation very challenging. The main objective of rehabilitation is, therefore, to ease the burden of symptoms by improving self-performance and independence. Inpatient, outpatient and Home rehabilitation with multidisciplinary team has been shown to be beneficial in improving disability. Individualized programs elaborated by a multidisciplinary team of experts are the key to success of rehabilitation. Family plays a big role and Family Based Rehabilitation will be important in long term rehab program in MS. PMID:26538848

  2. Mitochondrial dysfunction and neurodegeneration in multiple sclerosis

    PubMed Central

    Su, Kimmy; Bourdette, Dennis; Forte, Michael

    2013-01-01

    Multiple sclerosis (MS) has traditionally been considered an autoimmune inflammatory disorder leading to demyelination and clinical debilitation as evidenced by our current standard anti-inflammatory and immunosuppressive treatment regimens. While these approaches do control the frequency of clinical relapses, they do not prevent the progressive functional decline that plagues many people with MS. Many avenues of research indicate that a neurodegenerative process may also play a significant role in MS from the early stages of disease, and one of the current hypotheses identifies mitochondrial dysfunction as a key contributing mechanism. We have hypothesized that pathological permeability transition pore (PTP) opening mediated by reactive oxygen species (ROS) and calcium dysregulation is central to mitochondrial dysfunction and neurodegeneration in MS. This focused review highlights recent evidence supporting this hypothesis, with particular emphasis on our in vitro and in vivo work with the mitochondria-targeted redox enzyme p66ShcA. PMID:23898299

  3. [Multiple Sclerosis and Commensal Gut Flora].

    PubMed

    Yamamura, Takashi

    2016-06-01

    Although a symbiotic relationship between commensal gut microbiota and host is widely appreciated, recent works have indicated that normal gut flora functions to prevent inflammatory bowel diseases and obesity in the host, indicating a more mutualistic relationship. Dysbiosis of the commensal flora may lead to development of these disorders. Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS. PMID:27279159

  4. Involvement of mast cells in systemic sclerosis.

    PubMed

    Yukawa, Sonosuke; Yamaoka, Kunihiro; Sawamukai, Norifumi; Shimajiri, Shohei; Saito, Kazuyoshi; Tanaka, Yoshiya

    2010-01-01

    Systemic sclerosis is characterized by tissue fibrosis, obliterative microangiopathy and immune abnormalities. The etiology of SSc is largely unknown and is known to be resistant to existing corticosteroid and immunosuppressive drugs. Therefore, establishment of a treatment strategy especially for SSc patients with organ involvement is strongly desired. Mast cells are widely recognized as effector cells in allergic disorders and other IgE-mediated immune responses. However, recently, mast cells have become known to play a role in bridging innate immunity and adaptive immunity. Additionally, there is growing evidence of mast cell to be involved in pathogenesis of rheumatoid arthritis, and is expected as a novel therapeutic target. We describe here the role of mast cell in SSc pathology and suggest as a novel therapeutic target.

  5. Early systemic sclerosis-opportunities for treatment.

    PubMed

    Sakkas, Lazaros I; Simopoulou, Theodora; Katsiari, Christina; Bogdanos, Dimitrios; Chikanza, Ian C

    2015-08-01

    Systemic sclerosis (SSc) is characterized by microvasculopathy (Raynaud's phenomenon and fibrointimal proliferation), presence of autoantibodies and collagen deposition in skin (scleroderma) and internal organs. Microvasculopathy, detected by nailfold capillaroscopy, and disease-specific autoantibodies (anti-topoisomerase I, anti-centromere, anti-RNA polymerase III antibodies) usually appear earlier, even years before scleroderma. At that stage of the disease, immune activation with T cells and B cells promote fibrosis. Diagnosis of SSc has been relied on scleroderma, and by this time, internal organs may have developed fibrosis, a lethal feature with no available treatment. The new EULAR/ACR 2013 criteria for the classification of SSc will help identify SSc patients before fibrosis of internal organs. The early diagnosis of SSc, before the development of fibrosis in internal organs, will allow the introduction of immunosuppressive medications in these patients in a controlled setting (randomized trials). It is anticipated that this approach will change the hitherto grim prognosis of SSc for the better.

  6. Systemic sclerosis: An update in 2016.

    PubMed

    Desbois, Anne Claire; Cacoub, Patrice

    2016-05-01

    Systemic sclerosis (SSc) is a chronic immune disorder of unknown origin, dominated by excessive fibrosis responsible for cutaneous and pulmonary fibrosis, and by vascular endothelial dysfunction at the origin of skin ischemia, renal and pulmonary artery lesions. Renal and pulmonary complications are mainly responsible for the severity of the disease. Recent advances led to a better understanding of pathological mechanisms and a more accurate classification of patients according to clinical and biological (auto-antibodies) phenotype. Recent trials provided interesting data on different therapeutic strategies, depending on organ involvement. These data are of particular importance in such disease, still characterized by increased mortality and morbidity rates. In this review, we aim to synthetize recent advances in diagnosis and prognosis leading to better classification of SSc patients, and in therapeutic management.

  7. Amyotrophic lateral sclerosis and environmental factors

    PubMed Central

    Bozzoni, Virginia; Pansarasa, Orietta; Diamanti, Luca; Nosari, Guido; Cereda, Cristina; Ceroni, Mauro

    2016-01-01

    Summary Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that affects central and peripheral motor neuron cells. Its etiology is unknown, although a relationship between genetic background and environmental factors may play a major role in triggering the neurodegeneration. In this review, we analyze the role of environmental factors in ALS: heavy metals, electromagnetic fields and electric shocks, pesticides, β-N-methylamino-L-alanine, physical activity and the controversial role of sports. The literature on the single issues is analyzed in an attempt to clarify, as clearly as possible, whether each risk factor significantly contributes to the disease pathogenesis. After summarizing conflicting observations and data, the authors provide a final synthetic statement. PMID:27027889

  8. Quality of life in systemic sclerosis.

    PubMed

    Almeida, Cristiana; Almeida, Isabel; Vasconcelos, Carlos

    2015-12-01

    Systemic sclerosis (SSc) is a chronic multi-system autoimmune disease associated with disability and reduced quality of life. There is no effective treatment or cure to SSc, so it is important improve global health of these patients and reduce morbidity and mortality associated with SSc. It was made a literature review about quality of life in patients with SSc, regarding the several factors that should be considered and evaluated when attending to SSc patients. It was also considered the validated scales and questionnaires used to measure outcomes in patients with SSc. We concluded that it is important to have an interdisciplinary approach to SSc patients considering the patient's cognitive representations of the disease and what they value most like mobility and hand function, pain, fatigue, sleep, depression and body image.

  9. [Vision aids for multiple sclerosis patients].

    PubMed

    Frieling, E; Kornhuber, H H; Nissl, K

    1986-02-01

    Optical or electronic vision aids enabled 35 of 39 visually handicapped multiple sclerosis patients to read. Six patients had an uncorrected ametropia. 15 could read again with the help of magnifying optical aids and 11 with the help of an electronic television system. An electronic television reader was useful when visual acuities were below 0.1 and in patients with oscillating nystagmus or tremor capitis. Contact lenses helped 3 patients who had a neurogenous visual defect and oscillating nystagmus. Although acquired oscillating nystagmus disappears on eyelid closure and only reappears again on fixation, its amplitude, when unable to read, is greater. On overcoming the neurogenous visual defect with vision aids it becomes smaller.

  10. Renal manifestations of tuberous sclerosis complex.

    PubMed

    O'Hagan, A R; Ellsworth, R; Secic, M; Rothner, A D; Brouhard, B H

    1996-10-01

    Patients with tuberous sclerosis complex (TSC) are at increased risk of renal disease, predominantly angiomyolipomas and renal cysts. We retrospectively reviewed clinical data of 71 patients diagnosed with TSC. Progression of renal lesions was noted. TSC patients with renal lesions were compared with TSC patients without renal disease. Fifteen of 38 patients had renal abnormalities by imaging at presentation. Six of 9 with initially normal kidneys subsequently developed new lesions. Although not of statistical significance, there was a trend toward increased retinal hamartomas, cardiac rhabdomyomas, and skin lesions in those patients who also had renal abnormalities. Renal disease should be considered and sought in all patients with TSC, both at initial presentation and subsequently, since renal disease is a very significant cause of morbidity and mortality.

  11. Neurobehavioral burden of multiple sclerosis with nanotheranostics.

    PubMed

    Sriramoju, Bhasker; Kanwar, Rupinder K; Kanwar, Jagat R

    2015-01-01

    Multiple sclerosis (MS) is a chronic demyelinating neurological disorder affecting people worldwide; women are affected more than men. MS results in serious neurological deficits along with behavioral compromise, the mechanisms of which still remain unclear. Behavioral disturbances such as depression, anxiety, cognitive impairment, psychosis, euphoria, sleep disturbances, and fatigue affect the quality of life in MS patients. Among these, depression and psychosis are more common than any other neurological disorders. In addition, depression is associated with other comorbidities. Although anxiety is often misdiagnosed in MS patients, it can induce suicidal ideation if it coexists with depression. An interrelation between sleep abnormalities and fatigue is also reported among MS patients. In addition, therapeutics for MS is always a challenge because of the presence of the blood-brain barrier, adding to the lack of detailed understanding of the disease pathology. In this review, we tried to summarize various behavioral pathologies and their association with MS, followed by its conventional treatment and nanotheranostics.

  12. The 'Omics' of Amyotrophic Lateral Sclerosis.

    PubMed

    Caballero-Hernandez, Diana; Toscano, Miguel G; Cejudo-Guillen, Marta; Garcia-Martin, Maria L; Lopez, Soledad; Franco, Jaime M; Quintana, Francisco J; Roodveldt, Cintia; Pozo, David

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that primarily affects motor neurons and is accompanied by sustained unregulated immune responses, but without clear indications of the ultimate causative mechanisms. The identification of a diverse array of ALS phenotypes, a series of recently discovered mutations, and the links between ALS and frontotemporal degeneration have significantly increased our knowledge of the disease. In this review we discuss the main features involved in ALS pathophysiology in the context of recent advances in 'omics' approaches, including genomics, proteomics, and others. We emphasize the pressing need to combine clinical imaging with various different parameters taken from omics fields to facilitate early, accurate diagnosis and rational drug design in the treatment of ALS.

  13. Teriflunomide for oral therapy in multiple sclerosis.

    PubMed

    Papadopoulou, Athina; Kappos, Ludwig; Sprenger, Till

    2012-11-01

    Teriflunomide, the active metabolite of an approved antirheumatic drug, is an emerging oral therapy for multiple sclerosis (MS). Next to the inhibition of pyrimidine biosynthesis and proliferation of activated lymphocytes, it seems to have multiple anti-inflammatory and immunomodulating effects. Phase II and III clinical trials in relapsing MS demonstrated favorable safety and tolerability of the drug, as well as clinical efficacy, with a significant reduction of relapse rate, comparable with those of the available injectable immunomodulatory agents. While multiple other studies with teriflunomide are currently ongoing, its exact place in future treatment algorithms for MS is difficult to predict. It may be a good alternative for patients wishing to have an oral treatment with relatively large data regarding long-term safety. PMID:23234322

  14. Toward precision medicine in amyotrophic lateral sclerosis

    PubMed Central

    Liu, Chang-Yun; Che, Chun-Hui

    2016-01-01

    Precision medicine is an innovative approach that uses emerging biomedical technologies to deliver optimally targeted and timed interventions, customized to the molecular drivers of an individual’s disease. This approach is only just beginning to be considered for treating amyotrophic lateral sclerosis (ALS). The clinical and biological complexities of ALS have hindered development of effective therapeutic strategies. In this review we consider applying the key elements of precision medicine to ALS: phenotypic classification, comprehensive risk assessment, presymptomatic period detection, potential molecular pathways, disease model development, biomarker discovery and molecularly tailored interventions. Together, these would embody a precision medicine approach, which may provide strategies for optimal targeting and timing of efforts to prevent, stop or slow progression of ALS. PMID:26889480

  15. [Optic neuromyelitis. Main differences with multiple sclerosis].

    PubMed

    Lopategui Cabezas, I; Cervantes Llano, M; Pentón Rol, G

    2008-06-01

    The optic neuromyelitis or syndrome of Devic is an inflammatory and autoimmune illness of the central nervous system. It is characterized by attacks of optic neuritis and myelitis, being able to produce blindness, great neurological disability and even the short term death. Until the moment an effective treatment doesn't exist, the therapy is centred in the treatment of the acute attacks, the medical prevention of the complications and the rehabilitation. This article is a revision of this not very common illness, considering that its prevalence in our country has gone in increase. We compare between the optic neuromyelitis and the multiple sclerosis, being based on the main ones characteristic clinical-epidemic that distinguishes these two pathologies, considered by many clinical variants of oneself illness. PMID:19295979

  16. Magnetic resonance imaging in amyotrophic lateral sclerosis.

    PubMed

    Kollewe, Katja; Körner, Sonja; Dengler, Reinhard; Petri, Susanne; Mohammadi, Bahram

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder which is incurable to date. As there are many ongoing studies with therapeutic candidates, it is of major interest to develop biomarkers not only to facilitate early diagnosis but also as a monitoring tool to predict disease progression and to enable correct randomization of patients in clinical trials. Magnetic resonance imaging (MRI) has made substantial progress over the last three decades and is a practical, noninvasive method to gain insights into the pathology of the disease. Disease-specific MRI changes therefore represent potential biomarkers for ALS. In this paper we give an overview of structural and functional MRI alterations in ALS with the focus on task-free resting-state investigations to detect cortical network failures. PMID:22848820

  17. Progressive systemic sclerosis sine scleroderma in a child presenting as nocturnal seizures and Raynaud's phenomenon.

    PubMed

    Navon, P; Halevi, A; Brand, A; Branski, D; Rubinow, A

    1993-01-01

    Progressive systemic sclerosis sine scleroderma, as well as neurological manifestations of progressive systemic sclerosis are rare in adult-onset cases. Neither have been reported in children with progressive systemic sclerosis, either separately or together. We describe a six-year-old girl with nocturnal seizures and Raynaud's phenomenon of three years' duration. She died of cardiopulmonary sclerosis without ever fitting the required criteria of systemic sclerosis. Nailfold capillaroscopy revealed the specific "scleroderma-pattern" and provided the only clue for a diagnosis of progressive systemic sclerosis, confirmed eventually by skin biopsy.

  18. Clinical Usefulness of Aripiprazole and Lamotrigine in Schizoaffective Presentation of Tuberous Sclerosis

    PubMed Central

    Lee, Seung-Yup; Min, Jung-Ah; Lee, In Goo; Kim, Jung Jin

    2016-01-01

    Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis. PMID:27489387

  19. Total lymphoid irradiation for multiple sclerosis

    SciTech Connect

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one.

  20. Pelvic Floor Disorders and Multiple Sclerosis

    PubMed Central

    James, Rebecca; Frasure, Heidi

    2014-01-01

    Background: Despite recent efforts to educate multiple sclerosis (MS) health-care providers about the importance of pelvic floor disorders (urinary, bowel, and sexual dysfunction), no data are currently available to assess outcomes of these efforts in terms of patient satisfaction. Methods: As part of the fall 2010 North American Research Committee on Multiple Sclerosis survey, we conducted a prospective, survey-based cohort study (N = 14,268) to evaluate patient satisfaction with the current evaluation and treatment of pelvic floor disorders. Patients were queried about 1) bother from bladder, bowel, or sexual symptoms; 2) whether they had been evaluated by a health-care provider for pelvic floor issues in the last 12 months; and 3) satisfaction with the evaluation and treatment they received, on a 5-point Likert scale. Patients were also asked whether these treatments had affected their quality of life (7-point Likert scale). Results: A total of 9397 responses were received (response rate of 65.9%); respondents were primarily white (89%) and female (77.4%). Moderate-to-severe pelvic floor symptoms were reported by one-third of patients (bladder, 41%; bowel, 30%; sexual, 42%). Most respondents had been asked about bladder (61%) or bowel (50%) issues by their health-care providers, but only 20% had been queried about sexual dysfunction. Most respondents were moderately to very satisfied with the management of their bladder and bowel disorders but significantly less satisfied with that of sexual dysfunction. Conclusions: While MS patients are generally satisfied with current management of bladder and bowel dysfunction, improvement is needed in that of sexual dysfunction. PMID:24688351

  1. Steroids and brain atrophy in multiple sclerosis.

    PubMed

    Zivadinov, Robert

    2005-06-15

    In this review, we focus on different pathogenetic mechanisms of corticosteroids that induce short- and long-term brain volume fluctuations in a variety of systemic conditions and disorders, as well as on corticosteroid-induced immunomodulatory, immunosuppressive and anti-inflammatory mechanisms that contribute to the slowdown of brain atrophy progression in patients with multiple sclerosis (MS). It appears that chronic low-dose treatment with corticosteroids may contribute to irreversible loss of brain tissue in a variety of autoimmune diseases. This side effect of steroid therapy is probably mediated by steroid-induced protein catabolism mechanism. Evidence is mounting that high-dose corticosteroids may induce reversible short-term brain volume changes due to loss of intracellular water and reduction of abnormal vascular permeability, without there having been axonal loss. Other apoptotic and selective inhibiting mechanisms have been proposed to explain the nature of corticosteroid-induced brain volume fluctuations. It has been shown that chronic use of high dose intravenous methylprednisolone (IVMP) in patients with MS may limit brain atrophy progression over the long-term via different immunological mechanisms, including downregulation of adhesion molecule expression on endothelial cells, decreased cytokine and matrix metalloproteinase secretion, decreased autoreactive T-cell-mediated inflammation and T-cell apoptosis induction, blood-brain barrier closure, demyelination inhibition and, possibly, remyelination promotion. Studies in nonhuman primates have confirmed that short-term brain volume fluctuations may be induced by corticosteroid treatment, but that they are inconsistent, potentially reversible and probably dependent upon individual susceptibility to the effects of corticosteroids. Further longitudinal studies are needed to elucidate pathogenetic mechanisms contributing to brain volume fluctuations in autoimmune diseases and multiple sclerosis.

  2. Mitochondrial DNA sequence variation in multiple sclerosis

    PubMed Central

    Santaniello, Adam; Caillier, Stacy J.; D'Alfonso, Sandra; Martinelli Boneschi, Filippo; Hauser, Stephen L.; Oksenberg, Jorge R.

    2015-01-01

    Objective: To assess the influence of common mitochondrial DNA (mtDNA) sequence variation on multiple sclerosis (MS) risk in cases and controls part of an international consortium. Methods: We analyzed 115 high-quality mtDNA variants and common haplogroups from a previously published genome-wide association study among 7,391 cases from the International Multiple Sclerosis Genetics Consortium and 14,568 controls from the Wellcome Trust Case Control Consortium 2 project from 7 countries. Significant single nucleotide polymorphism and haplogroup associations were replicated in 3,720 cases and 879 controls from the University of California, San Francisco. Results: An elevated risk of MS was detected among haplogroup JT carriers from 7 pooled clinic sites (odds ratio [OR] = 1.15, 95% confidence interval [CI] = 1.07–1.24, p = 0.0002) included in the discovery study. The increased risk of MS was observed for both haplogroup T (OR = 1.17, 95% CI = 1.06–1.29, p = 0.002) and haplogroup J carriers (OR = 1.11, 95% CI = 1.01–1.22, p = 0.03). These haplogroup associations with MS were not replicated in the independent sample set. An elevated risk of primary progressive (PP) MS was detected for haplogroup J participants from 3 European discovery populations (OR = 1.49, 95% CI = 1.10–2.01, p = 0.009). This elevated risk was borderline significant in the US replication population (OR = 1.43, 95% CI = 0.99–2.08, p = 0.058) and remained significant in pooled analysis of discovery and replication studies (OR = 1.43, 95% CI = 1.14–1.81, p = 0.002). No common individual mtDNA variants were associated with MS risk. Conclusions: Identification and validation of mitochondrial genetic variants associated with MS and PPMS may lead to new targets for treatment and diagnostic tests for identifying potential responders to interventions that target mitochondria. PMID:26136518

  3. Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

    ERIC Educational Resources Information Center

    Mackenzie, Catherine; Green, Jan

    2009-01-01

    Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

  4. 38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was...

  5. 38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was...

  6. 38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was...

  7. 38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was...

  8. 38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was...

  9. Gastric Antral Vascular Ectasia in Systemic Sclerosis: Current Concepts

    PubMed Central

    Parrado, Raphael Hernando; Lemus, Hernan Nicolas; Coral-Alvarado, Paola Ximena; Quintana López, Gerardo

    2015-01-01

    Introduction. Gastric antral vascular ectasia (GAVE) is a rare entity with unique endoscopic appearance described as “watermelon stomach.” It has been associated with systemic sclerosis but the pathophysiological changes leading to GAVE have not been explained and still remain uncertain. Methods. Databases Medline, Scopus, Embase, PubMed, and Cochrane were searched for relevant papers. The main search words were “Gastric antral vascular ectasia,” “Watermelon Stomach,” “GAVE,” “Scleroderma,” and “Systemic Sclerosis.” Fifty-four papers were considered for this review. Results. GAVE is a rare entity in the spectrum of manifestations of systemic sclerosis with unknown pathogenesis. Most patients with systemic sclerosis and GAVE present with asymptomatic anemia, iron deficiency anemia, or heavy acute gastrointestinal bleeding. Symptomatic therapy and endoscopic ablation are the first-line of treatment. Surgical approach may be recommended for patients who do not respond to medical or endoscopic therapies. Conclusion. GAVE can be properly diagnosed and treated. Early diagnosis is key in the management of GAVE because it makes symptomatic therapies and endoscopic approaches feasible. A high index of suspicion is critical. Future studies and a critical review of the current findings about GAVE are needed to understand the role of this condition in systemic sclerosis. PMID:26633973

  10. Tomography patterns of lung disease in systemic sclerosis*

    PubMed Central

    Bastos, Andréa de Lima; Corrêa, Ricardo de Amorim; Ferreira, Gilda Aparecida

    2016-01-01

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses.

  11. How can proteomics elucidate the complexity of multiple sclerosis?

    PubMed

    Farias, Alessandro S; Santos, Leonilda M B

    2015-10-01

    Multiple sclerosis affects more than 2.5 million people worldwide. Although multiple sclerosis was described almost 150 years ago, there are many knowledge gaps regarding its etiology, diagnosis, prognosis, and pathogenesis. Multiple sclerosis is an inflammatory, demyelinating, neurodegenerative disease of the CNS. During the last several decades, experimental models of multiple sclerosis have contributed to our understanding of the inflammatory disease mechanisms and have aided drug testing and development. However, little is known about the neurodegenerative mechanisms that operate during the evolution of the disease. Currently, all therapeutic approaches are primarily based on the inflammatory aspect of the disease. During the last decade, proteomics has emerged as a promising tool for revealing molecular pathways as well as identifying and quantifying differentially expressed proteins. Therefore, proteomics may be used for the discovery of biomarkers, potential drug targets, and new regulatory mechanisms. To date, a considerable number of proteomics studies have been conducted on samples from experimental models and patients with multiple sclerosis. These data form a solid base for further careful analysis and validation.

  12. Vision and vision-related outcome measures in multiple sclerosis.

    PubMed

    Balcer, Laura J; Miller, David H; Reingold, Stephen C; Cohen, Jeffrey A

    2015-01-01

    Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

  13. "Abnormal" illness behaviour in chronic fatigue syndrome and multiple sclerosis.

    PubMed Central

    Trigwell, P.; Hatcher, S.; Johnson, M.; Stanley, P.; House, A.

    1995-01-01

    OBJECTIVE--To investigate the presence of abnormal illness behaviour in patients with a diagnosis of chronic fatigue syndrome. DESIGN--A cross sectional descriptive study using the illness behaviour questionnaire to compare illness behaviour scores and illness behaviour profiles of patients with chronic fatigue syndrome and patients with multiple sclerosis. SETTING--A multidisciplinary fatigue clinic and a teaching hospital neurology outpatient clinic. SUBJECTS--98 patients satisfying the Oxford criteria for chronic fatigue syndrome and 78 patients with a diagnosis of multiple sclerosis. MAIN OUTCOME MEASURE--Responses to the 62 item illness behaviour questionnaire. RESULTS--90 (92%) patients in the chronic fatigue syndrome group and 70 (90%) in the multiple sclerosis group completed the illness behaviour questionnaire. Both groups had significantly high scores on the general hypochondriasis and disease conviction subscales and significantly low scores on the psychological versus somatic concern subscale, as measured in relation to normative data. There were, however, no significant differences in the subscale scores between the two groups and the two groups had identical illness behaviour profiles. CONCLUSION--Scores on the illness behaviour questionnaire cannot be taken as evidence that chronic fatigue syndrome is a variety of abnormal illness behaviour, because the same profile occurs in multiple sclerosis. Neither can they be taken as evidence that chronic fatigue and multiple sclerosis share an aetiology. More needs to be known about the origins of illness beliefs in chronic fatigue syndrome, especially as they are important in determining outcome. PMID:7613314

  14. Vision and vision-related outcome measures in multiple sclerosis.

    PubMed

    Balcer, Laura J; Miller, David H; Reingold, Stephen C; Cohen, Jeffrey A

    2015-01-01

    Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.

  15. Lockhart Clarke's contribution to the description of amyotrophic lateral sclerosis.

    PubMed

    Turner, Martin R; Swash, Michael; Ebers, George C

    2010-11-01

    The definition of the clinicopathological entity of amyotrophic lateral sclerosis evolved over half a century. Although the definitive term amyotrophic lateral sclerosis that acknowledged both upper and lower motor neuron involvement was attributed to Jean-Martin Charcot in 1874, his initial case was published nearly a decade earlier; and it is accepted that, from at least the 1830s, several others (including Charles Bell, François-Amilcar Aran and Jean Cruveilhier) had already recognized a progressive lower motor neuron-only syndrome within a broader, clinically-defined group of disorders, termed progressive muscular atrophy. Although William Gowers first grouped the three phenotypes of amyotrophic lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy together as part of the same syndrome, the term motor neuron disease, as an over-arching label, was not suggested until nearly a century later by W. Russell Brain. Augustus Jacob Lockhart Clarke (1817-80) is best known for his descriptions of spinal cord anatomy. However, in two detailed case reports from the 1860s, he carried out rigorous post-mortem neuropathological studies of what appear to be classical cases of amyotrophic lateral sclerosis. Furthermore, he recognized the additional involvement of the corticospinal tracts that distinguished this from progressive muscular atrophy. Several aspects of the exquisite clinical histories documented as part of both studies, one by Charles Bland Radcliffe, resonate with contemporary debates concerning the evolution of disease in amyotrophic lateral sclerosis. These 'past masters' still have much to teach us.

  16. Uphill and Downhill Walking in Multiple Sclerosis

    PubMed Central

    Samaei, Afshin; Hajihasani, Abdolhamid; Fatemi, Elham; Motaharinezhad, Fatemeh

    2016-01-01

    Background: Various exercise protocols have been recommended for patients with multiple sclerosis (MS). We investigated the effects of uphill and downhill walking exercise on mobility, functional activities, and muscle strength in MS patients. Methods: Thirty-four MS patients were randomly allocated to either the downhill or uphill treadmill walking group for 12 sessions (3 times/wk) of 30 minutes' walking on a 10% negative slope (n = 17) or a 10% positive slope (n = 17), respectively. Measurements were taken before and after the intervention and after 4-week follow-up and included fatigue by Modified Fatigue Impact Scale; mobility by Modified Rivermead Mobility Index; disability by Guy's Neurological Disability Scale; functional activities by 2-Minute Walk Test, Timed 25-Foot Walk test, and Timed Up and Go test; balance indices by Biodex Balance System; and quadriceps and hamstring isometric muscles by torque of left and right knee joints. Analysis of variance with repeated measures was used to investigate the intervention effects on the measurements. Results: After the intervention, significant improvement was found in the downhill group versus the uphill group in terms of fatigue, mobility, and disability indices; functional activities; balance indices; and quadriceps isometric torque (P < .05). The results were stable at 4-week follow-up. Conclusions: Downhill walking on a treadmill may improve muscle performance, functional activity, and balance control in MS patients. These findings support the idea of using eccentric exercise training in MS rehabilitation protocols. PMID:26917996

  17. [Central hyperacusis with phonophobia in multiple sclerosis].

    PubMed

    Pfadenhauer, K; Weber, H; Rösler, A; Stöhr, M

    2001-12-01

    Auditory disturbances are a well known symptom in patients with multiple sclerosis (MS). Uni- or bilateral hypacusis or deafness in patients with normal auditory testing is considered to be a result of lesions in the central auditory pathway. Only rarely described is a central phonophobia whereby acoustic stimuli induce unpleasant and painful perceptions, with consecutive avoidance of these factors. Our first patient described acute shooting pain in the right cheek, triggered only through the ringing of a telephone. The second patient had uncomfortable perception of nonverbal noise. For example the wrinkling of paper bags was unbearable for him. The third patient had difficulties localizing the source of sound and disturbing echos while listening to speech or music. Clinically, in all patients symptoms of a brainstem syndrome were found, whereas auditory testing including inspection, audiometry, and stapedius reflex was normal. We found pathological acoustic evoked potentials (AEP) in all three patients with a prolonged latency III-V and T2 lesions in the ipsilateral pons and central auditory pathway. In case one, we suppose a lateral spread between the lateral lemniscus and the central trigeminal pathway. In the other cases, a dysfunction of the central sensory modulation which controls the regulation of sensitivity of incoming acoustic stimuli seems to be the cause of hyperacusis. All our patients developed clinically confirmed MS in the further course after suffering from phonophobia as their first symptom.

  18. Tuberous sclerosis with visceral organ involvement.

    PubMed

    See, J S; Shen, E Y; Chiu, N C; Ho, C S; Lee, Y L; Chen, M R; Tsai, J D

    1999-01-01

    This study is to determine the incidence of visceral organ involvement in tuberous sclerosis (TS). We reviewed 30 cases of TS diagnosed between 1987 to 1997. There were 17 males and 13 females, ages ranged from one day old to 17 years old. Among the 30 cases, 25 patients had seizures and skin manifestations; 24 had cerebral tubercles; 10 had heart involvement (9 rhabdomyoma, 1 dilated cardiomyopathy); 4 had kidney involvement (3 polycystic kidney disease, 1 renal hamartoma); and 3 had retinal astrocytic hamartoma. Based on our study, the most common visceral organs involved were the heart and kidney. Among the ten patients with cardiac rhabdomyoma, six were less than 1 year old (mean age 1.6 +/- 2.2 years old). One newborn presented with a cardiac mass diagnosed by prenatal sonography and another newborn, noted to have tachycardia after birth, underwent surgical intervention due to impending heart failure. Four patients had kidney abnormalities; three were less than 5 years old (mean age 5.2 +/- 5.2 years). During this 10 year period, there was no mortality seen among patients with visceral organ involvement. We suggest that clinicians treating patients with TS should not overlook the visceral organs, especially heart and kidney, which, if involved can have significant morbidity. PMID:10910538

  19. Impaired Cognitive Flexibility in Amyotrophic Lateral Sclerosis

    PubMed Central

    Evans, Jessica; Olm, Christopher; McCluskey, Leo; Elman, Lauren; Boller, Ashley; Moran, Eileen; Rascovsky, Katya; Bisbing, Teagan; McMillan, Corey T.; Grossman, Murray

    2014-01-01

    Objective Up to half of patients with amyotrophic lateral sclerosis (ALS) may have cognitive difficulty, but most cognitive measures are confounded by a motor component. Rare studies have related impaired cognition in ALS to disease in gray matter (GM) and white matter (WM). We evaluated a simple, untimed measure of executive functioning with minimal motor demands in ALS, and relate performance to structural disease. Methods Fifty-six patients with ALS and 29 matched healthy controls were assessed with the Visual-Verbal Test (VVT). This brief measure of cognitive flexibility first assesses an individual's ability to identify a shared feature in three of four simple geometric designs. Cognitive flexibility is challenged when individuals are next asked to identify a different shared feature in another three of the same four geometric designs. Regression analyses related performance to GM atrophy and reduced WM fractional anisotropy (FA) in a subset of patients. Results ALS patients were significantly impaired on this simple measure of cognitive flexibility (p<0.01). An error in cognitive flexibility was present in 48.2% of individual ALS patients. Regression analyses related impaired cognitive flexibility to GM atrophy in inferior frontal and insula regions, and to reduced FA in WM projections in inferior frontal-occipital and uncinate fasciculi and corpus callosum. Conclusion Patients with ALS have impaired cognitive flexibility on an untimed measure with minimal motor demands, and this is related in part to a large-scale frontal network that is degraded in ALS. PMID:25812127

  20. Characteristics of pain in amyotrophic lateral sclerosis

    PubMed Central

    Hanisch, Frank; Skudlarek, Anika; Berndt, Janine; Kornhuber, Malte E

    2015-01-01

    Background Pain is an often underestimated and neglected symptom in amyotrophic lateral sclerosis (ALS). Methods In a cross-sectional survey, 46 patients with ALS, 46 age- and gender matched population-based controls, and 23 diseased controls with myotonic dystrophy type 2 (DM2) were screened for occurrence, type, distribution, and treatment of pain and cramps. Data were collected with the use of the short form brief pain inventory (BPI). Results Pain was reported in 78% of ALS patients,79% of DM2 patients, and 54% of controls (P < 0.05). More ALS patients than controls reported moderate to severe pain (42% vs. 20%). Pain in ALS patients interfered significantly more with daily activities than in controls (median pain interference score: 3.0 vs. 1.2, P < 0.05), especially enjoyment of life (5.0 vs. 1.0) and mood (3.0 vs. 1.0). There was no correlation between the duration of the disease and the severity of pain. Movement-induced cramps were reported in 63% of ALS patients, mostly in the distal extremities. There was no difference in the duration of ALS disease between patients reporting cramps and those who did not. Discussion Our study showed that pain was a relatively frequent symptom which had an important impact on the quality of life. Pain that requires treatment can occur at every stage of ALS. PMID:25642388

  1. The topographical model of multiple sclerosis

    PubMed Central

    Cook, Karin; De Nino, Scott; Fletcher, Madhuri

    2016-01-01

    Relapses and progression contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity has been fully characterized. A hypothesis-driven, biologically informed model could build on the clinical phenotypes to encompass the dynamic admixture of factors underlying MS disease course. In this medical hypothesis, we put forth a dynamic model of MS disease course that incorporates localization and other drivers of disability to propose a clinical manifestation framework that visualizes MS in a clinically individualized way. The topographical model encapsulates 5 factors (localization of relapses and causative lesions; relapse frequency, severity, and recovery; and progression rate), visualized utilizing dynamic 3-dimensional renderings. The central hypothesis is that, like symptom recrudescence in Uhthoff phenomenon and pseudoexacerbations, progression clinically recapitulates prior relapse symptoms and unmasks previously silent lesions, incrementally revealing underlying lesion topography. The model uses real-time simulation software to depict disease course archetypes and illuminate several well-described but poorly reconciled phenomena including the clinical/MRI paradox and prognostic significance of lesion location and burden on disease outcomes. Utilization of this model could allow for earlier and more clinically precise identification of progressive MS and predictive implications can be empirically tested.

  2. Pediatric multiple sclerosis: Cognition and mood.

    PubMed

    Amato, Maria Pia; Krupp, Lauren B; Charvet, Leigh E; Penner, Iris; Till, Christine

    2016-08-30

    In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of age-expected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and mood-related difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research.

  3. Imaging of Multiple Sclerosis: Role in Neurotherapeutics

    PubMed Central

    Bakshi, Rohit; Minagar, Alireza; Jaisani, Zeenat; Wolinsky, Jerry S.

    2005-01-01

    Summary: Magnetic resonance imaging (MRI) plays an ever-expanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normal-appearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1- or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics. PMID:15897951

  4. Interstitial lung disease in systemic sclerosis.

    PubMed

    Wells, Athol U

    2014-10-01

    Based on international collaborative data, interstitial lung disease is now the most frequent cause of death in systemic sclerosis (SSc), having supplanted renal crisis in that regard. Despite detailed explorations of candidate mediators, no primary pathway in the pathogenesis of interstitial lung disease associated with SSc (SSc-ILD) has been definitively identified and, therefore, treatment with current agents is only partially successful. However, as immunomodulatory agents do, on average, retard progression of lung disease, early identification of SSc-ILD, using thoracic high resolution computed tomography (HRCT), is highly desirable. The decision whether to introduce therapy immediately is often difficult as the balance of risk and benefit favours a strategy of careful observation when lung disease is very limited, especially in long-standing SSc. The threshold for initiating treatment is substantially reduced when lung disease is severe, systemic disease is short in duration or ongoing progression is evident, based on pulmonary function tests and symptoms. This review summarises epidemiology, pathogenesis, difficult clinical problems and management issues in SSc-ILD.

  5. Emerging immunopharmacological targets in multiple sclerosis.

    PubMed

    Farjam, Mojtaba; Zhang, Guang-Xian; Ciric, Bogoljub; Rostami, Abdolmohamad

    2015-11-15

    Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate in relapsing-remitting MS (RRMS), the prevention of long-term accumulation of deficits remains a challenge. Medications used for progressive forms of MS also have limited efficacy. The need for therapies that are effective against disease progression continues to drive the search for novel pharmacological targets. In recent years, due to a better understanding of MS immunopathogenesis, new approaches have been introduced that more specifically target autoreactive immune cells and their products, thus increasing specificity and efficacy, while reducing potential side effects such as global immunosuppression. In this review we describe several immunopharmacological targets that are currently being explored for MS therapy. PMID:26440421

  6. Overview and diagnosis of multiple sclerosis.

    PubMed

    Hunter, Samuel F

    2016-06-01

    Multiple sclerosis (MS), a chronic inflammatory disease of unknown etiology, involves an immunemediated attack of the central nervous system (CNS) that produces demyelination and axonal/neuronal damage, resulting in characteristic multifocal lesions apparent on magnetic resonance imaging and a variety of neurologic manifestations. The disease pathology is characterized by multifocal lesions within the CNS, in both the white matter and gray matter, with perivenular inflammatory cell infiltrates, demyelination, axonal transection, neuronal degeneration, and gliosis. MS pathogenesis is complex, as it involves both T- and B-cell mechanisms and is heterogeneous in presentation. Relatively recently, the historical 4 core clinical categories of MS were revised in an effort to improve characterization of the clinical course, better identify where a given patient is positioned in the disease spectrum, and to guide clinical studies. In young and middle-aged adults, MS is one of the most common contributors to neurologic disability, and it exerts detrimental effects on a patient's productivity and health-related quality of life. Typically, patients with MS have a long life span, although healthcare utilization increases over time. As a consequence, the disease places a substantial burden on patients and their caregivers/families, as well as employers, the healthcare system, and society. PMID:27356023

  7. Evidence for genetic heterogeneity in tuberous sclerosis.

    PubMed Central

    Sampson, J R; Yates, J R; Pirrit, L A; Fleury, P; Winship, I; Beighton, P; Connor, J M

    1989-01-01

    The question of genetic heterogeneity in tuberous sclerosis (TSC) was addressed by genetic linkage studies in eight affected families using nine polymorphic markers (EFD126.3, MCT136, ABO, ABL, AK1, and MCOA12 from distal 9q, and PBGD, MCT128.1, and 1CJ52.208M from distal 11q). The data as a whole supported a TSC locus on distal 9q, the peak lod score on multipoint analysis being 3.77 at 6 cM proximal to the Abelson oncogene locus (ABL). However, analysis of two point lod scores using the HOMOG programs showed significant evidence for genetic heterogeneity (p = 0.01), linkage to ABL being unlikely in one family. After exclusion of the unlinked family, multipoint analysis gave a peak lod score of 6.1 in the vicinity of ABL. The family unlinked to ABL showed no recombinants with two chromosome 11 probes, but was too small to provide significant evidence for linkage. Genetic heterogeneity in TSC will complicate efforts to clone the causative genes and severely limit the use of linked probes for carrier detection and prenatal diagnosis. PMID:2769723

  8. Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities

    PubMed Central

    Miljković, Djordje; Spasojević, Ivan

    2013-01-01

    Abstract The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286–2334. PMID:23473637

  9. Multiple sclerosis care in Latin America.

    PubMed

    Rivera, Victor M; Medina, Marco Tulio; Duron, Reyna M; Macias, Miguel Angel

    2014-05-01

    Before the advent of diagnostic criteria for multiple sclerosis (MS), it was reported that the prevalence of MS in Mexico was "one of the lowest in the world" (1.6/100,000).(1) The notion that MS was a rare neurologic disease among those living in the tropics of the Americas and Southern latitudes was widely accepted. The geopolitical boundaries of the region identified as Latin America (LA) extend from the southern border of United States with Mexico (32° North latitude) to the Argentinian and Chilean Patagonia in South America (56° South latitude). The largest Spanish-speaking island countries in the Caribbean-Cuba, Dominican Republic, and Puerto Rico-are also traditionally considered part of LA. The continental mass includes 17 countries with a population of more than 550 million. Due to centuries of racial intermixing, it is a heterogeneous and genetically complex population. The blended cultures of native Amerindians with white Caucasian Europeans and black Africans has resulted in the predominant ethnic Latin American Mestizo. The influence of African genetics is notable in many areas of the subcontinent and the Caribbean. A common observation across LA is the absence of identification of MS in non-mixed Amerindians(2); the reason for this phenomenon is unclear.

  10. Matrix metalloproteinases and neuroinflammation in multiple sclerosis.

    PubMed

    Rosenberg, Gary A

    2002-12-01

    Matrix metalloproteinases (MMPs) are extracellular matrix remodeling neutral proteases that are important in normal development, angiogenesis, wound repair, and a wide range of pathological processes. Growing evidence supports a key role of the MMPs in many neuroinflammatory conditions, including meningitis, encephalitis, brain tumors, cerebral ischemia, Guillain-Barré, and multiple sclerosis (MS). The MMPs attack the basal lamina macromolecules that line the blood vessels, opening the blood-brain barrier (BBB). They contribute to the remodeling of the blood vessels that causes hyalinosis and gliosis, and they attack myelin. During the acute inflammatory phase of MS, they are involved in the injury to the blood vessels and may be important in the disruption of the myelin sheath and axons. Normally under tight regulation, excessive proteolytic activity is detected in the blood and cerebrospinal fluid in patients with acute MS. Because they are induced in immunologic and nonimmunologic forms of demyelination, they act as a final common pathway to exert a "bystander" effect. Agents that block the action of the MMPs have been shown to reduce the damage to the BBB and lead to symptomatic improvement in several animal models of neuroinflammatory diseases, including experimental allergic encephalomyelitis. Such agents may eventually be useful in the control of excessive proteolysis that contributes to the pathology of MS and other neuroinflammatory conditions.

  11. Narrative discourse deficits in amyotrophic lateral sclerosis

    PubMed Central

    Menaged, Anna; Olm, Christopher; McMillan, Corey T.; Boller, Ashley; Irwin, David J.; McCluskey, Leo; Elman, Lauren; Grossman, Murray

    2014-01-01

    Objective: We examined narrative discourse in amyotrophic lateral sclerosis (ALS) to assess the role of executive functioning in support of language and the neuroanatomical basis for such support. Methods: We analyzed a semistructured speech sample in 26 patients with ALS and 19 healthy seniors for narrative discourse features of coherence. Regression analyses related a measure of discourse coherence (“local connectedness”) to gray matter atrophy and reduced white matter fractional anisotropy. Results: Patients with ALS were impaired relative to controls on measures of discourse adequacy, including local connectedness and maintenance of the theme. These discourse measures were related to measures of executive functioning but not to motor functioning. Regressions related local connectedness to gray matter atrophy in ventral and dorsal prefrontal regions and to reduced fractional anisotropy in white matter tracts mediating projections between prefrontal regions. Conclusion: Patients with ALS exhibit deficits in their ability to organize narrative discourse. These deficits appear to be related in part to executive limitations. Consistent with the hypothesis that ALS is a multisystem disorder, this deficit is related to disease in prefrontal regions. PMID:24991038

  12. [Restorative therapy in amyotrophic lateral sclerosis].

    PubMed

    Aoki, Masashi

    2012-11-01

    Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder characterized by the death of upper and lower motor neurons. About 10% of all ALS cases are familial; approximately 20% of familial ALS cases are caused by mutations in the superoxide dismutase 1 (SOD1) gene. We developed rats that express a human SOD1 transgene with ALS-associated mutations, developing striking motor neuron degeneration and paralysis. The larger size of this rat model as compared with the ALS mice, will facilitate studies involving manipulations of spinal fluid and the spinal cord. Hepatocyte growth factor (HGF) is one of the most potent survival-promoting factors for motor neurons. We administered human recombinant HGF (hrHGF) by continuous intrathecal delivery to the transgenic rats at the onset of paralysis for 4 weeks. Intrathecal administration of hrHGF attenuated motor neuron degeneration and prolonged the duration of the disease by 63%. To translate this strategy to human treatment, we induced a contusive cervical spinal cord injury in the common marmoset, a primate, and then administered hrHGF intrathecally. The intrathecal administration of hrHGF promoted functional recovery. These results prompted further clinical trials in ALS using continuous intrathecal administration of hrHGF. PMID:23373317

  13. [Epidemiology of multiple sclerosis in Tiumen' region].

    PubMed

    Sivertseva, S A; Zhuravlev, M N; Murav'ev, S A; Boĭko, A N

    2006-01-01

    Prevalence of multiple sclerosis (MS) was evaluated in the pilot study of 731 patients living in Tyumen city and a southern part of Tyumen region as well as in Khanty-Mansi (KMAO) and Yamal-Nenets (YNAO) autonomic okrugs. An index of MS prevalence was 22,4 per 100,000 in Tyumen region as a whole. This index was higher--29.1 per 100 000 - in the southern part. In KMAO and YNAO, the MS prevalence was 14,3 and 27,8 respectively. Women prevailed among patients in all the regions, their number being twice higher (461 and 270). However, if in the southern part and in KMAO this ratio was approximately equal, in YNAO percentage of men was significantly higher. It should be noted that these data need further study. We revealed that using of current diagnostic criteria may often lead to misunderstanding of diagnosis of "definite" MS. Essential difference in MS prevalence in different regions may be explained by ethnical stratification. In particular, there are many newly migrated people in the okrugs and MS occurs more often in that group. At the same time, there is no any information on the prevalence of "definite" MS among the native-born population of KMAO and YNAO.

  14. Coronary angiographic findings in asymptomatic systemic sclerosis.

    PubMed

    Tarek, El-Gohary; Yasser, Amin E; Gheita, Tamer

    2006-07-01

    The objective of this study was to assess coronary arterial involvement in asymptomatic systemic sclerosis (SSc) patients. Fourteen female patients with SSc (five limited and nine diffuse) were recruited for this study. All patients fulfilled the following 1980 American College of Rheumatology criteria for classification of SSc Masi et al (Arthritis Rheum 23:581-590 1980). None of them had chest pain nor electrocardiogram (ECG) changes suggestive of myocardial ischemia. All patients underwent thorough history taking, full clinical examination, routine laboratory investigations, and basic screening for conventional atherosclerotic disease risk factors. ECG and coronary catheterization were done for all patients. We detected 19 coronary angiographic abnormalities in our cohort. Three out of nine diffuse SSc patients (33.33%) had ectasia of the coronary arteries, and all of them had slow flow but none in the limited type. One patient with limited SSc showed spasm. Three out of five patients with limited type (60%) had stenosis, one of them had uncontrolled hypertension, while none of the diffuse type had. Five patients (55.55%) of the diffuse type had tortuosity, while it was found in only two patients (40%) of the limited type. Three patients (33.3%) of the diffuse type had calcification of the coronaries, while it was seen in two patients (40%) of the limited type. Pathological involvement of coronary arteries in asymptomatic SSc patients is not uncommon but not paralleled by clinical symptomatology.

  15. Olfactory dysfunction in patients with multiple sclerosis.

    PubMed

    Li, Li-Min; Yang, Li-Na; Zhang, Lin-Jie; Fu, Ying; Li, Ting; Qi, Yuan; Wang, Jing; Zhang, Da-Qi; Zhang, Ningnannan; Liu, Jingchun; Yang, Li

    2016-06-15

    Association of changes in olfactory-related structures with olfactory function in patients with multiple sclerosis (MS) is not well understood. We used a T&T olfactometer test kit to evaluate olfactory function in 26 patients with MS and 26 age- and sex-matched healthy controls (HC). Then, Brain MRI were performed and olfactory-related structures were analyzed in these subjects. Olfactory detection and recognition threshold were significantly higher in the MS group, interestingly olfactory recognition threshold positively correlated with expanded disability status scale scores in these patients. Olfactory bulb (OB) volume reduced in patients with olfactory dysfunction (ODF). At the same time, reductions in gray matter (GM) volume were observed in the parahippocampal gyrus (PCG), amygdala, piriform cortex, and inferior frontal gyrus in patients with MS compared to HC. Atrophy of the PCG was more obvious in patients with ODF than patients without ODF and the PCG volume correlated with the olfactory recognition threshold, while no difference was found in fractional anisotropy values of tract-based spatial statistics analysis in the two groups. Olfactory function in patients with MS tends to become gradually more impaired with disability aggravation. Decreases in the volume of the OB and olfactory-related GM might provide valuable information about disease status in patients with MS with olfactory impairment. PMID:27206870

  16. A basic overview of multiple sclerosis immunopathology.

    PubMed

    Grigoriadis, N; van Pesch, V

    2015-10-01

    Multiple sclerosis (MS) is a multi-component disease characterized by inflammation, neurodegeneration and failure of central nervous system (CNS) repair mechanisms. Immune dysregulation appears to originate with dendritic cells (antigen-presenting cells) which have an activated phenotype in individuals with MS. Dendritic cells migrate across the blood-brain barrier and induce differentiation of memory T cells into pro-inflammatory T helper 1 (Th1) and Th17 lymphocytes. In turn, induction of macrophage and microglial activation produces other pro-inflammatory cytokines and oxygen and nitric oxide radicals responsible for the demyelination and axonal loss. Other known mediators of MS pathology include CD8+ T cells and memory B cells within the CNS. Some pathological hallmarks of MS are early axonal degeneration and progressive decline of brain volume in patients with clinically isolated syndromes who progress to clinically definite MS. Many new options to interfere with the course of MS have become available in recent years. To limit inflammatory demyelinating processes and delay disease progression, intervention to control inflammation must begin as early as possible. Each distinct type of immunotherapy (immunomodulation, immunosuppression and immune-selective intervention - blockade type, sequestering type or depleting type) corresponds to a specific underlying immunopathology of MS.

  17. Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis.

    PubMed

    Neppelberg, E; Haugen, D F; Thorsen, L; Tysnes, O-B

    2007-12-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Sialorrhea is a frequent problem in ALS patients with bulbar symptoms, because of progressive weakness of oral, lingual and pharyngeal muscles. This prospective study aimed to investigate the putative effect of palliative single-dose radiotherapy on problematic sialorrhea in patients with ALS. Twenty patients with ALS and problematic drooling were included; 14 were given radiotherapy with a single fraction of 7.5 Grey (Gy). Five patients were treated with botulinum toxin A (BTX-A) injections (20 U) into the parotid glands; two of these were later given radiotherapy. Symptom assessment, clinical examination and measurements of salivary flow (ml/min) were performed before and after treatment (1-2 weeks, 3 months). Salivary secretion was significantly reduced after radiation treatment, with a mean reduction of 60% (1 week) and 51% (2 weeks). Three months post-treatment, 21% reduction of the salivary secretion was observed compared with salivation before treatment. Mean salivary flow was not reduced after BTX-A treatment in five patients. No serious side-effects were observed with either of the two treatment modalities. Single-dose radiotherapy (7.5 Gy) significantly reduces sialorrhea and is an effective and safe palliative treatment in patients with ALS.

  18. Emotional Perception Deficits in Amyotrophic Lateral Sclerosis

    PubMed Central

    Zimmerman BA, Erin K.; Eslinger PhD, Paul J.; MD, Zachary Simmons; Barrett MD, Anna M.

    2007-01-01

    Objective Cognitive deficits associated with frontal lobe dysfunction can occur in amyotrophic lateral sclerosis (ALS), particularly in individuals with bulbar ALS who can also suffer pathological emotional lability. Since frontal pathophysiology can alter emotional perception, we examined whether emotional perception deficits occur in ALS, and whether they are related to depressive or dementia symptoms. Methods Bulbar ALS participants (n = 13) and age-matched healthy normal controls (n = 12) completed standardized tests of facial and prosodic emotional recognition, the Geriatric Depression Scale, and the Mini-Mental State Examination. Participants identified the basic emotion (happy, sad, angry, afraid, surprised, disgusted) that matched 39 facial expressions and 28 taped, semantically neutral, intoned sentences. Results ALS patients performed significantly worse than controls on facial emotional recognition but not on prosodic emotional recognition. Eight of 13 patients (62%) scored below the 95% Confidence Interval of controls in recognizing facial emotions, and 3 of these patients (23% overall) also scored lower in prosody recognition. Among the 8 patients with emotional perceptual impairment, one-half did not have depressive, or memory or cognitive symptoms on screening, while the remainder showed dementia symptoms alone or together with depressive symptoms. Conclusions Emotional recognition deficits occur in bulbar ALS, particularly with emotional facial expressions, and can arise independent of depressive and dementia symptoms or co-morbid with depression and dementia. These findings expands the scope of cognitive dysfunction detected in ALS, and bolsters the view of ALS as a multisystem disorder involving cognitive as well as motor deficits. PMID:17558250

  19. Noise in multiple sclerosis: unwanted and necessary

    PubMed Central

    Bordi, Isabella; Ricigliano, Vito A G; Umeton, Renato; Ristori, Giovanni; Grassi, Francesca; Crisanti, Andrea; Sutera, Alfonso; Salvetti, Marco

    2014-01-01

    As our knowledge about the etiology of multiple sclerosis (MS) increases, deterministic paradigms appear insufficient to describe the pathogenesis of the disease, and the impression is that stochastic phenomena (i.e. random events not necessarily resulting in disease in all individuals) may contribute to the development of MS. However, sources and mechanisms of stochastic behavior have not been investigated and there is no proposed framework to incorporate nondeterministic processes into disease biology. In this report, we will first describe analogies between physics of nonlinear systems and cell biology, showing how small-scale random perturbations can impact on large-scale phenomena, including cell function. We will then review growing and solid evidence showing that stochastic gene expression (or gene expression “noise”) can be a driver of phenotypic variation. Moreover, we will describe new methods that open unprecedented opportunities for the study of such phenomena in patients and the impact of this information on our understanding of MS course and therapy. PMID:25356421

  20. Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

    PubMed Central

    Shi, Ping; Gal, Jozsef; Kwinter, David M.; Liu, Xiaoyan; Zhu, Haining

    2009-01-01

    The etiology of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains to be better understood. Based on the studies from ALS patients and transgenic animal models, it is believed that ALS is likely to be a multifactorial and multisystem disease. Many mechanisms have been postulated to be involved in the pathology of ALS, such as oxidative stress, glutamate excitotoxicity, mitochondrial damage, defective axonal transport, glia cell pathology and aberrant RNA metabolism. Mitochondria, which play crucial roles in excitotoxicity, apoptosis and cell survival, have shown to be an early target in ALS pathogenesis and contribute to the disease progression. Morphological and functional defects in mitochondria were found in both human patients and ALS mice overexpressing mutant SOD1. Mutant SOD1 was found to be preferentially associated with mitochondria and subsequently impair mitochondrial function. Recent studies suggest that axonal transport of mitochondria along microtubules and mitochondrial dynamics may also be disrupted in ALS. These results also illustrate the critical importance of maintaining proper mitochondrial function in axons and neuromuscular junctions, supporting the emerging “dying-back” axonopathy model of ALS. In this review, we will discuss how mitochondrial dysfunction has been linked to the ALS variants of SOD1 and the mechanisms by which mitochondrial damage contributes to the disease etiology. PMID:19715760

  1. Cognitive dysfunction in pediatric multiple sclerosis

    PubMed Central

    Suppiej, Agnese; Cainelli, Elisa

    2014-01-01

    Cognitive and neuropsychological impairments are well documented in adult multiple sclerosis (MS). Research has only recently focused on cognitive disabilities in pediatric cases, highlighting some differences between pediatric and adult cases. Impairments in several functions have been reported in children, particularly in relation to attention, processing speed, visual–motor skills, and language. Language seems to be particularly vulnerable in pediatric MS, unlike in adults in whom it is usually preserved. Deficits in executive functions, which are considered MS-specific in adults, have been inconsistently reported in children. In children, as compared to adults, the relationship between cognitive dysfunctions and the two other main symptoms of MS, fatigue and psychiatric disorders, was poorly explored. Furthermore, data on the correlations of cognitive impairments with clinical and neuroimaging features are scarce in children, and the results are often incongruent; interestingly, involvement of corpus callosum and reduced thalamic volume differentiated patients identified as having a cognitive impairment from those without a cognitive impairment. Further studies about pediatric MS are needed in order to better understand the impact of the disease on brain development and the resulting effect on cognitive functions, particularly with respect to different therapeutic strategies. PMID:25092984

  2. The Transition to Secondary Progressive Multiple Sclerosis

    PubMed Central

    Wood, Fiona; Brain, Katherine E.; Edwards, Michelle; Jones, Rhiannon; Wallbank, Rachel; Robertson, Neil P.; Edwards, Adrian

    2016-01-01

    Background: Identifying the transition from relapsing-remitting to secondary progressive multiple sclerosis (SPMS) can be challenging for clinicians. Little previous research has explored how professionals experience working with patients during this specific stage of the disease. We explored the experiences of a group of multidisciplinary professionals who support patients in the transition to SPMS to describe this stage from a professional perspective. Methods: This qualitative semistructured interview study included 11 professionals (medical, nursing, and allied health professionals; specialists and generalists) working with patients with MS in South Wales, United Kingdom. Thematic analysis of the interview data was performed. Results: Two overarching themes were identified: the transition and providing support. The transition theme comprised issues related to recognizing and communicating about SPMS. Uncertainty influenced recognizing the transition and knowing how to discuss it with patients. The providing support theme included descriptions of challenging aspects of patient care, providing support for caregivers, using the multidisciplinary team, and working within service constraints. Providing adequate psychological support and engaging patients with self-management approaches were seen as particularly challenging. Conclusions: Caring for patients in the transition to SPMS generates specific challenges for professionals. Further research on health-care interactions and patients'/professionals' experiences regarding the transition phase may help identify strategies for professional development and learning and how to optimize the patient experience at this difficult stage of disease. PMID:27803641

  3. Amyotrophic Lateral Sclerosis: New Perpectives and Update

    PubMed Central

    Orsini, Marco; Oliveira, Acary Bulle; Nascimento, Osvaldo J.M.; Reis, Carlos Henrique Melo; Leite, Marco Antonio Araujo; de Souza, Jano Alves; Pupe, Camila; de Souza, Olivia Gameiro; Bastos, Victor Hugo; de Freitas, Marcos R.G.; Teixeira, Silmar; Bruno, Carlos; Davidovich, Eduardo; Smidt, Benny

    2015-01-01

    Amyotrophic lateral sclerosis (ALS), Charcot’s disease or Lou Gehrig’s disease, is a term used to cover the spetrum of syndromes caracterized by progressive degeneration of motor neurons, a paralytic disorder caused by motor neuron degeneration. Currently, there are approximately 25,000 patients with ALS in the USA, with an average age of onset of 55 years. The incidence and prevalence of ALS are 1-2 and 4-6 per 100,000 each year, respectively, with a lifetime ALS risk of 1/600 to 1/1000. It causes progressive and cumulative physical disabilities, and leads to eventual death due to respiratory muscle failure. ALS is diverse in its presentation, course, and progression. We do not yet fully understand the causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. In this chapter, we will discuss the diagnosis, treatment, and how to cope with impaired function and end of life based on of our experience, guidelines, and clinical trials. Nowadays ALS seems to be a more complex disease than it did two decades – or even one decade – ago, but new insights have been plentiful. Clinical trials should be seen more as experiments on pathogenic mechanisms. A medication or combination of medications that targets more than one pathogenic pathway may slow disease progression in an additive or synergistic fashion. PMID:26487927

  4. The topographical model of multiple sclerosis

    PubMed Central

    Cook, Karin; De Nino, Scott; Fletcher, Madhuri

    2016-01-01

    Relapses and progression contribute to multiple sclerosis (MS) disease course, but neither the relationship between them nor the spectrum of clinical heterogeneity has been fully characterized. A hypothesis-driven, biologically informed model could build on the clinical phenotypes to encompass the dynamic admixture of factors underlying MS disease course. In this medical hypothesis, we put forth a dynamic model of MS disease course that incorporates localization and other drivers of disability to propose a clinical manifestation framework that visualizes MS in a clinically individualized way. The topographical model encapsulates 5 factors (localization of relapses and causative lesions; relapse frequency, severity, and recovery; and progression rate), visualized utilizing dynamic 3-dimensional renderings. The central hypothesis is that, like symptom recrudescence in Uhthoff phenomenon and pseudoexacerbations, progression clinically recapitulates prior relapse symptoms and unmasks previously silent lesions, incrementally revealing underlying lesion topography. The model uses real-time simulation software to depict disease course archetypes and illuminate several well-described but poorly reconciled phenomena including the clinical/MRI paradox and prognostic significance of lesion location and burden on disease outcomes. Utilization of this model could allow for earlier and more clinically precise identification of progressive MS and predictive implications can be empirically tested. PMID:27648465

  5. Pediatric multiple sclerosis: Escalation and emerging treatments.

    PubMed

    Chitnis, Tanuja; Ghezzi, Angelo; Bajer-Kornek, Barbara; Boyko, Alexey; Giovannoni, Gavin; Pohl, Daniela

    2016-08-30

    Over the last 20 years, there have been significant advances in multiple sclerosis (MS) therapeutics, with regulatory approval for 13 therapies in adults by the European Medicines Agency (EMA) and Food and Drug Administration. However, there is only limited approval for interferon-β and glatiramer acetate use in children 12 years and older by the EMA. Availability of disease-modifying therapies to children and adolescents with MS is variable by region, and is extremely limited in some regions of the world. Up to 30% of children experience breakthrough disease requiring therapies beyond traditional first-line agents. Recent legislation in both the United States and Europe has mandated clinical studies for all new therapeutics applicable to children. Several clinical trials in children are underway that will provide important information regarding the efficacy and safety of newer drugs. This review summarizes the current knowledge of breakthrough disease, escalation, and induction treatment approaches in children with MS, especially pertaining to disease course and disability outcomes in this group of patients. In addition, ongoing clinical trials and approaches and challenges in conducting clinical trials in the pediatric population are discussed.

  6. Systemic sclerosis: from pathogenesis to targeted therapy.

    PubMed

    Denton, Christopher P

    2015-01-01

    Systemic sclerosis (scleroderma) leads to morbidity and mortality through a combination of inflammation, fibrosis and vascular damage leading to internal organ complications affecting the heart, lung, kidneys and bowel. More than half of those diagnosed ultimately die from the disease. Current treatments focus on broad spectrum immunosuppression or organ-based therapy for complication such as lung fibrosis, pulmonary or systemic hypertension. Targeting peptide mediators such as endothelin-1 have already led to licensed effective therapies for SSc vasculopathy. Outcomes are improving but as well as providing a major clinical challenge there are great opportunities for research translation that can be expected to improve understanding of the pathogenesis of SSc and also develop better and more targeted therapy. Key pathways and mediators can be identified within the skin and blood vessels and these are now being examined in early stage clinical trials. Promising results are emerging from targeting cytokine signalling, including IL-6, and from other immune-inflammatory therapies including lipid mediators such as LPA1. Other approaches to modulate TGFbeta and other profibrotic pathways also have potential although safety and toxicity remain to be determined. Since many profibrotic pathways have important physiological roles the assessment of safety and toxicity will be paramount. Nevertheless, advances in understanding the interplay between different pathological processes and progress in clinical trial design and patients stratification mean that targeted therapies are emerging and likely to be further developed and refined to have application in other important clinical contexts such as lung fibrosis.

  7. The symptomatic management of multiple sclerosis

    PubMed Central

    Schapiro, Randall T.

    2009-01-01

    The management of multiple sclerosis (MS) revolves around disease management, symptom management, and person management. Of these, symptom management takes up the bulk of the time of the practicing physician. Some symptoms are easily managed whereas others are more difficult. Decisions have often to be made on whether to treat or to wait and watch. This article discusses the varied symptoms of MS and the approaches to management, which involves rehabilitation, pharmacological treatments, and surgical procedures. The skilled physician managing MS should be familiar with the multiple approaches to improving the quality of life of those with MS. After the diagnosis has been established and the decisions regarding treatment approaches have been made, the talk in a typical office appointment for MS usually turns to symptom management. Thus, the majority of management decisions made by the clinician revolve around that important topic. It is symptom management that will determine quality of life for those with MS, It is the basis for improving function, and, up until twenty years ago, it was the only basis for treating MS. Now, however, we can approach treatment by disease management, symptom management, and person management. The MS specialist must be well versed in all three areas. PMID:20182577

  8. Systemic sclerosis: markers and targeted treatments.

    PubMed

    Cutolo, M; Sulli, A; Pizzorni, C; Paolino, S; Smith, V

    2016-01-01

    Systemic sclerosis (SSc) is characterized by autoantibody production, progressive microvasculopathy, and aberrant extracellular matrix protein (ECM) synthesis in tissues. The disease presents two major clinical hallmarks: Raynaud's phenomenon (RP) and skin involvement, followed by varying prevalences of internal organ involvement. Despite significant advances in the management of certain organ-specific involvements and symptoms, the research for efficient markers and targets, to be used for an optimized treatment, is still ongoing. Therapies targeting the vasculature (i.e. ET-1 receptor antagonists, phosphodiesterase-5 (PDE-5) inhi bitor, agiotensin-converting enzyme inhibition, prostacyclins), the immune system and/or the fibrotic process (i.e. traditional disease modifying anti-rheu - matic drugs DMARDs such as methotrexate, cyclospo - rine or mycophenolate mofetil, biologicals like rituxi - mab, tocilizumab or abatacept) have been or are being eva luated in SSc. Advanced approaches, reserved to unres ponsive SSc patients, include autologous haema - topoietic stem cell transplantation (HSTC) and intravenous immunoglobulins (IVIG). Interestingly, it is expected that new and future possible diagnostic and therapeutical approaches in SSc will come from epigenetic studies (MicroRNAs). Ideally, combination therapy in SSc seems the best approach, together with the early intervention on the major hallmarks of the disease in "at risk" patients, that consists of the microvascular damage/altered function and the autoimmune reaction, followed by the progressive and systemic fibrotic process.

    . PMID:27115104

  9. Natalizumab in multiple sclerosis: proceed with caution?

    PubMed

    Doggrell, Sheila A

    2006-08-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the CNS. In a Phase II clinical trial, natalizumab was shown to reduce the relapses in patients with relapsing MS, without improving the disability score. After 1-year of Phase III clinical trials, natalizumab was approved by the FDA for use in relapsing MS but was withdrawn 3 months later, due to two reported cases of progressive multifocal leukoencephalopathy (PML). The completed clinical trials with natalizumab for relapsing MS have recently been reported. In a trial of 1171 subjects with relapsing MS, natalizumab alone was shown to reduce the relapse rate and lesions, without causing PML. Although natalizumab was also shown to reduce the relapse rates and lesions in patients taking IFN-beta, two cases of PML with natalizumab occurred in these patients. An assessment of patients who had taken natalizumab for 1 - 2 years (approximately 3000), showed the incidence of PML to be 1/1000. A drug that is useful in relapsing MS will be used as a long-term therapy in large numbers of patients. For instance, in the 3 months that natalizumab was registered, 5000 patients commenced taking it. In the author's opinion, large numbers of patients should not be allowed to take natalizumab until its safety has been monitored in the long-term use in a clinical trial environment.

  10. Multiple sclerosis susceptibility alleles in African Americans

    PubMed Central

    Johnson, Britt A.; Wang, Joanne; Taylor, Elise M.; Caillier, Stacy J.; Herbert, Joseph; Khan, Omar A.; Cross, Anne H.; De Jager, Philip L.; Gourraud, Pierre-Antoine F.; Cree, Bruce C.A.; Hauser, Stephen L.; Oksenberg, Jorge R.

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disease characterized by complex genetics and multifaceted gene-environment interactions. Compared to whites, African Americans have a lower risk for developing MS, but African Americans with MS have a greater risk of disability. These differences between African Americans and whites may represent differences in genetic susceptibility and/or environmental factors. SNPs from 12 candidate genes have recently been identified and validated with MS risk in white populations. We performed a replication study using 918 cases and 656 unrelated controls to test whether these candidate genes are also associated with MS risk in African Americans. CD6, CLEC16a, EVI5, GPC5, and TYK2 contained SNPs that are associated with MS risk in the African American dataset. EVI5 showed the strongest association outside the MHC (rs10735781, OR = 1.233, 95% CI = 1.06–1.43, P value = 0.006). In addition, RGS1 appears to affect age of onset whereas TNFRSF1A appears to be associated with disease progression. None of the tested variants showed results that were statistically in-consistent with the effects established in whites. The results are consistent with shared disease genetic mechanisms among individuals of European and African ancestry. PMID:19865102

  11. Emerging oral agents for multiple sclerosis.

    PubMed

    Fox, Edward J

    2010-09-01

    A variety of emerging therapies for the treatment of multiple sclerosis (MS) are currently in development or have recently been approved by the US Food and Drug Administration (FDA). These new agents offer novel mechanisms of action and potentially improved efficacy over existing first-line MS therapies. Much attention has been given to emerging therapies delivered orally which, at minimum, will likely improve long-term adherence over existing agents delivered via injection. This article reviews the mechanisms of action, efficacy, and safety and tolerability of 4 emerging oral therapies for MS: cladribine, laquinimod, fingolimod, and dalfampridine. The first 3 of these agents are in late development and may enter the market within the next year and a half. Cladribine, laquinimod, and fingolimod have demonstrated impressive efficacy in terms of clinical outcomes, such as annualized relapse rate and change in disability scores, as well as magnetic resonance imaging variables. Dalfampridine, which has already been approved by the FDA, is indicated as a symptomatic therapy to improve walking in MS patients. Based on existing data, these agents appear to have tolerable side-effect profiles, although the long-term safety profiles of these drugs have yet to be elucidated. It remains to be seen whether the safety profiles of these disease-modifying drugs will allow them to displace existing first-line therapies or if agents such as dalfampridine will become additional options alongside current dominant therapies.

  12. Epidemiologic correlates of sporadic amyotrophic lateral sclerosis

    SciTech Connect

    Armon, C.; Kurland, L.T.; Daube, J.R.; O'Brien, P.C. )

    1991-07-01

    The authors evaluated 74 selected patients with amyotrophic lateral sclerosis (ALS) and 201 matched controls for risk factors for ALS by a case-control design and a sequential questionnaire/interview technique to quantitate biographic data. They analyzed occupational and recreational data only for 47 male patients and 47 corresponding patient controls; data for women were insufficient. They used nonparametric analyses to evaluate five primary comparisons of ALS patients with controls: (1) more hard physical labor, p not significant (NS); (2) greater frequency of neurodegenerative disease in family members, p NS; (3) greater exposure to lead, p less than 0.05; (4) more years lived in a rural community, p NS; and (5) more trauma or major surgery, p NS. Men with ALS had worked more frequently at blue-collar jobs (although not a statistically significant difference, p = 0.10) and at welding or soldering (p less than 0.01). These results suggest that there may be an association between ALS in men and exposure to lead vapor. The limited nature of the association favors a multifactorial etiologic mechanism of ALS.

  13. Pediatric multiple sclerosis: Escalation and emerging treatments.

    PubMed

    Chitnis, Tanuja; Ghezzi, Angelo; Bajer-Kornek, Barbara; Boyko, Alexey; Giovannoni, Gavin; Pohl, Daniela

    2016-08-30

    Over the last 20 years, there have been significant advances in multiple sclerosis (MS) therapeutics, with regulatory approval for 13 therapies in adults by the European Medicines Agency (EMA) and Food and Drug Administration. However, there is only limited approval for interferon-β and glatiramer acetate use in children 12 years and older by the EMA. Availability of disease-modifying therapies to children and adolescents with MS is variable by region, and is extremely limited in some regions of the world. Up to 30% of children experience breakthrough disease requiring therapies beyond traditional first-line agents. Recent legislation in both the United States and Europe has mandated clinical studies for all new therapeutics applicable to children. Several clinical trials in children are underway that will provide important information regarding the efficacy and safety of newer drugs. This review summarizes the current knowledge of breakthrough disease, escalation, and induction treatment approaches in children with MS, especially pertaining to disease course and disability outcomes in this group of patients. In addition, ongoing clinical trials and approaches and challenges in conducting clinical trials in the pediatric population are discussed. PMID:27572854

  14. Unusual ocular motor findings in multiple sclerosis.

    PubMed

    de Seze, J; Vukusic, S; Viallet-Marcel, M; Tilikete, C; Zéphir, H; Delalande, S; Stojkovic, T; Defoort-Dhellemmes, S; Confavreux, C; Vermersch, P

    2006-04-15

    In multiple sclerosis (MS), nystagmus or internuclear ophthalmoplegia (INO) are the usual ocular motor dysfunctions. However, in patients with focal brainstem lesions, other rare manifestations may be observed, such as an isolated ocular motor nerve palsy or complex ocular motor disturbances. We report five MS patients with unusual ocular motor disturbances (bilateral third nerve palsy [n = 2], opsoclonus, Horner's syndrome and one-and-a-half syndrome). We discuss possible correlations between clinical disturbances and MRI abnormalities. Patients were seen in two MS centres. They had a confirmed diagnosis of MS and underwent a brain MRI and a complete neuro-ophthalmological work-up. In one case (opsoclonus), ocular motor manifestations were the first manifestation of MS. In the other four cases they occurred 3 months (Horner syndrome), 6 years and 12 years (bilateral third nerve palsy) and 2 years (one-and-a-half syndrome) after the disease onset, respectively. Four out of five patients were still in a relapsing-remitting form of MS. In the opsoclonus case, there was no evidence of a brainstem lesion. A gadolinium-enhanced lesion (2 cases) or a new T2-weighted lesion located in the brainstem correlated with the clinical presentation. All patients completely or partially recovered after corticosteroid infusions. Our study shows some rare or previously undescribed complex ocular motor symptoms in MS. PMID:16466746

  15. [Immunotherapies for multiple sclerosis : review and update].

    PubMed

    Havla, J; Kümpfel, T; Hohlfeld, R

    2015-04-01

    Multiple sclerosis (MS) is an inflammatory, presumably autoimmune disease affecting the central nervous system. Early stages of the disease are characterized by conspicuous inflammation of the white and grey matter. During later stages, presumably secondary neurodegeneration leads to physical disability progression. Over the last decade increasingly effective therapeutic options have been approved. Currently 11 immunomodulatory or immunosuppressive therapies targeting relapse rate, disease progression and paraclinical disease activity are available, mostly for relapsing forms of MS. However, the ideal of "precision medicine" is still in the distant future since biomarkers for individualized treatment are lacking. For implementation of risk-management plans to minimize the risk of severe side effects, interdisciplinary collaboration between neurologists and internists is essential. In this review article we summarize practical aspects of the implemented risk-management plans, and discuss possible side effects and special caveats of the three new immunotherapies teriflunomide, dimethyl fumarate, and alemtuzumab. This article is based on, among others, the recently updated guidelines of the German Society of Neurology. Particular attention is given to the risks of new therapies, monitoring, and on special aspects needing attention when changing treatments. Teriflunomide, dimethyl fumarate, and alemtuzumab expand treatment options for relapsing-remitting MS. Treatment selection should take into consideration the safety profile of the substance, previous and concomitant diseases, and other individual factors. This requires in-depth consultation and individual assessment of current disease activity, the potential efficacy of the therapy, and the possible risks and side effects. PMID:25720530

  16. [Teriflunomide for treatment of multiple sclerosis].

    PubMed

    Warnke, C; Meyer Zu Hörste, G; Menge, T; Stüve, O; Hartung, H-P; Wiendl, H; Kieseier, B C

    2013-06-01

    Interferon beta and glatiramer acetate are still considered to be the first-line therapeutics for treatment of relapsing forms of multiple sclerosis (MS). The use of new compounds, such as natalizumab or fingolimod, is restricted to severe forms of relapsing MS or cases refractory to first-line treatment owing to substance-specific risk-benefit considerations. Teriflunomide is a new compound which has recently been approved as a first-line treatment of relapsing forms of MS in the USA and Australia. It is characterized by a once daily oral administration and a comparably well-established long-term safety profile. The main therapeutic effect is considered to be mediated via the inhibition of the de novo synthesis of pyrimidine in proliferating immune cells. The pro-drug of teriflunomide, leflunomide, has a label for treating rheumatoid arthritis (RA) for many years. Two recently published phase III clinical trials (TEMSO, TOWER) tested teriflunomide in patients with relapsing forms of MS and efficacy was demonstrated, with positive effects on relapse rates and disease progression using 14 mg/day. Overall, the safety profile in these studies was favorable as expected from experiences with leflunomide in RA. In patients treated with teriflunomide regular monitoring of blood cell counts and liver enzymes is required. Teriflunomide must not be used during pregnancy. In this article the recent phase II and phase III clinical trial data are reviewed and the potential of teriflunomide for the treatment of relapsing forms of MS is discussed. PMID:23695001

  17. Multiple sclerosis: a primary care perspective.

    PubMed

    Saguil, Aaron; Kane, Shawn; Farnell, Edwin

    2014-11-01

    Multiple sclerosis (MS) is the most common permanently disabling disorder of the central nervous system in young adults. Relapsing remitting MS is the most common type, and typical symptoms include sensory disturbances, Lhermitte sign, motor weakness, optic neuritis, impaired coordination, and fatigue. The course of disease is highly variable. The diagnosis is clinical and involves two neurologic deficits or objective attacks separated in time and space. Magnetic resonance imaging is helpful in confirming the diagnosis and excluding mimics. Symptom exacerbations affect 85% of patients with MS. Corticosteroids are the treatment of choice for patients with acute, significant symptoms. Disease-modifying agents should be initiated early in the treatment of MS to forestall disease and preserve function. Two immunomodulatory agents (interferon beta and glatiramer) and five immunosuppressive agents (fingolimod, teriflunomide, dimethyl fumarate, natalizumab, and mitoxantrone) are approved by the U.S. Food and Drug Administration for the treatment of MS, each with demonstrated effectiveness and unique adverse effect profiles. Symptom management constitutes a large part of care; neurogenic bladder and bowel, sexual dysfunction, pain, spasticity, and fatigue are best treated with a multidisciplinary approach to improve quality of life. PMID:25368924

  18. Disease-modifying agents in multiple sclerosis.

    PubMed

    O'Connor, Paul W; Oh, Jiwon

    2014-01-01

    Over the past two decades, major advances have been made in the development of disease-modifying agents (DMAs) for multiple sclerosis (MS), and nine agents are now licensed for use in the treatment of MS in the United States. Clinical trials have demonstrated that a number of investigational agents have beneficial effects on clinical and radiographic measures of disease activity, thus the repertoire of available DMAs in MS will likely continue to expand moving forward. Although many of the first-line DMAs have the benefits of established long-term safety and tolerability, in some patients, treatment with one of the more potent novel agents may be appropriate. However, the use of novel agents must be approached with caution, since short-term clinical trials give little information on the long-term efficacy and safety of novel DMAs in MS patients. This chapter will consider the efficacy and safety of both established and investigational agents for the treatment of MS. PMID:24507532

  19. Induction and escalation therapies in multiple sclerosis.

    PubMed

    Fenu, G; Lorefice, L; Frau, F; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system. Pharmacological therapy of MS includes symptomatic drugs, treatment for relapses (corticosteroid and intravenous immunoglobulin) and disease modifying drugs (DMDs) defined as pharmacological agents that have an impact on relapse rate, disability accumulation and radiological outcomes. Two different therapeutic approaches are widely used in MS: escalation and induction therapy. Escalation therapy consists of an early start with first line DMDs (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate) and if DMDs are ineffective or partially effective, switching to second line drugs (mitoxantrone, natalizumab, fingolimod). Induction therapy consists of the early use of immunosuppressant drugs followed by long-term maintenance treatment, generally with immunomodulatory agents. While the use of natalizumab and fingolimod as first line drugs is indicated for aggressive forms of MS, the indication for mitoxantrone as an induction treatment arises from randomized studies demonstrating that induction therapy with mitoxantrone followed by DMD maintenance is more effective than monotherapy with beta interferon. However, the safety profile of induction drugs indicates this is not an acceptable therapeutic strategy for all MS patients in all phases of the disease. The upcoming challenge is to identify patients at high risk of disability development from their clinical characteristics, radiological findings or biomarkers. Furthermore, future studies to establish an individual safety profile stratification are needed. PMID:25938688

  20. The epidemiology of amyotrophic lateral sclerosis.

    PubMed

    Talbott, E O; Malek, A M; Lacomis, D

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults and is characterized by neurodegeneration of motor neurons in the brain and spinal cord. The incidence of ALS is approximately 1-2.6 cases per 100 000 persons annually, whereas the prevalence is approximately 6 cases per 100 000. The average age of onset of ALS is currently 58-60 years and the average survival from onset to death is 3-4 years. Between October 19, 2010 and December 31, 2011, there were an estimated 12 187 prevalent cases diagnosed with definite ALS in the USA alone. Sporadic ALS (90-95%) constitutes the large majority of cases, while the remaining 5-10% are hereditary and termed familial ALS. Sporadic ALS is suspected to involve genetic susceptibility to environmental risk factors. The purpose of this review is to present a clinical overview of ALS and provide an epidemiologic summary of personal and environmental risk factors shown to be related to the risk of disease. A discussion of the most recent research initiatives is also included. PMID:27637961

  1. Controversies and priorities in amyotrophic lateral sclerosis

    PubMed Central

    Turner, Martin R; Hardiman, Orla; Benatar, Michael; Brooks, Benjamin R; Chio, Adriano; de Carvalho, Mamede; Ince, Paul G; Lin, Cindy; Miller, Robert G; Mitsumoto, Hiroshi; Nicholson, Garth; Ravits, John; Shaw, Pamela J; Swash, Michael; Talbot, Kevin; Traynor, Bryan J; den Berg, Leonard H Van; Veldink, Jan H; Vucic, Steve; Kiernan, Matthew C

    2015-01-01

    Summary Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events. PMID:23415570

  2. [Medical-social aspects of multiple sclerosis].

    PubMed

    Vermersch, P; Marissal, J P

    2001-09-01

    On a daily basis the quality of life of patients suffering from multiple sclerosis (MS) partially depends on social measures. These are not specific to MS. Patients often need to be helped by hospital or town social services for the numerous and complicated administrative steps to be taken. The information given to a patient is of prime importance concerning his rights, particularly his occupational rights. Many organisations have to be contacted to obtain financial and material aids, even if the latter are considered insufficient in many fields especially for improvements in accommodation. An invalidity card may entitle its holder to certain tax reductions. The competences of the COTOREP are wide-ranging and include the recognition of the handicapped worker, his training and his regarding at work, his orientation and admission into a specialised structure, the degree of his invalidity rate and should his handicap justify it, benefits such as the handicapped adults allowance and the compensatory third person's allowance. It is essential to adopt a multidisciplinary way when dealing with MS in order to provide a better care, experiments in specialised structures and networks are being undertaken. Numerous partners are taking part in these new approaches and patient associations may find their place there. Social aspects have to be taken into account as well in the way the cost of the disease is evaluated in terms of money and humanity. PMID:11787351

  3. Decisional Capacity in Amyotrophic Lateral Sclerosis.

    PubMed

    Khin Khin, Eindra; Minor, Darlinda; Holloway, Amanda; Pelleg, Ayla

    2015-06-01

    The cognitive and behavioral changes that can be observed in the neurodegenerative terminal disease amyotrophic lateral sclerosis (ALS), once characterized as purely a motor neuron disease, have become increasingly recognized over the past century. Detecting cognitive deficits earlier and identifying continued changes at regular intervals can lead to improved care, proactive treatments, and earlier discussions about end-of-life wishes. Although medical decisional capacity is required for every treatment decision made, its importance becomes paramount when making decisions on complex medical treatments that will invariably and significantly affect quality of life or life itself. In this review, we conducted a critical analysis of the evidence-based literature on the cognitive and behavioral impairments in ALS that can compromise medical decisional capacity. We review specific ALS-related clinical scenarios in which decisional capacity is of utmost importance and discuss a practical framework for cognitive and behavioral assessment that can be routinely and efficiently used, while being mindful of the confounding factors associated with ALS. Finally, we review models for preserving patient choices that can be used in patients with ALS to help safeguard autonomy and retain dignity toward the end of life. PMID:26071511

  4. Altered Cortical Communication in Amyotrophic Lateral Sclerosis

    PubMed Central

    Blain-Moraes, Stefanie; Mashour, George A.; Lee, Heonsoo; Huggins, Jane E.; Lee, UnCheol

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a disorder associated primarily with the degeneration of the motor system. More recently, functional connectivity studies have demonstrated potentially adaptive changes in ALS brain organization, but disease-related changes in cortical communication remain unknown. We recruited individuals with ALS and age-matched controls to operate a brain-computer interface while electroencephalography was recorded over three sessions. Using normalized symbolic transfer entropy, we measured directed functional connectivity from frontal to parietal (feedback connectivity) and parietal to frontal (feedforward connectivity) regions. Feedback connectivity was not significantly different between groups, but feedforward connectivity was significantly higher in individuals with ALS. This result was consistent across a broad electroencephalographic spectrum (4 – 35 Hz), and in theta, alpha and beta frequency bands. Feedback connectivity has been associated with conscious state and was found to be independent of ALS symptom severity in this study, which may have significant implications for the detection of consciousness in individuals with advanced ALS. We suggest that increases in feedforward connectivity represent a compensatory response to the ALS-related loss of input such that sensory stimuli have sufficient strength to cross the threshold necessary for conscious processing in the global neuronal workspace. PMID:23567743

  5. Pediatric multiple sclerosis: Cognition and mood.

    PubMed

    Amato, Maria Pia; Krupp, Lauren B; Charvet, Leigh E; Penner, Iris; Till, Christine

    2016-08-30

    In comparison with the large body of evidence on cognitive functioning in adults with multiple sclerosis (MS), there is limited information on cognition in pediatric-onset MS (POMS). Unique vulnerabilities in POMS can derive from having a disease that occurs during key periods of age-expected brain growth, active myelination in the CNS, and maturation of neural networks during the learning curve and key formative years in the academic career of the patient. Therefore, the consequences of MS on developing cognitive faculties can be assessed only in the pediatric population and cannot be simply extrapolated from studies carried on in the adult population. Until the last decade, research in the pediatric population was mainly represented by small clinical series, often limited by the narrow scope of neuropsychological assessment and lack of adequate control groups. Over the last decade, however, cognitive functioning and mood-related difficulties have become an increasing concern as awareness of this population has grown. A few specialized MS centers have begun performing more systematic research in the field in order to assess the prevalence of cognitive impairments and mood-related difficulties in patients with POMS, to better characterize the neuropsychological pattern and determine the functional consequences of these problems. This chapter summarizes our current understanding of cognitive and mood-related difficulties in POMS and highlights perceived gaps in knowledge and priorities for future research. PMID:27572867

  6. Husbands and wives living with multiple sclerosis.

    PubMed

    Courts, Nancy Fleming; Newton, Amanda N; McNeal, Linda J

    2005-02-01

    Multiple sclerosis (MS) frequently is diagnosed in young adults. Coping with symptoms of MS is challenging not only for the person with the disease, but also for his or her spouse. The well spouse often assumes the caregiving role. The purpose of this qualitative research was to investigate the experiences of persons whose spouses have MS. Twelve people participated in a 2-hour focus group: 8 men and 4 women. The husbands were, on average, 50 years old, and the wives averaged 55 years old. The length of time since diagnosis ranged from 2 to 11 years for the husbands and from 3 to 13 years for the wives. The focus group discussions were audiotaped and transcribed verbatim. Participants talked freely. Four major themes emerged: caregiver roles, need for information, relationship changes, and barriers. Men attempted to protect their wives' energy, intervening for them. Wives encouraged independence in their husbands. Spouses need information about MS, complementary interventions, and support. They want increased public awareness of invisible symptoms and awareness in the workplace of continuing capabilities of persons with MS. Role reversals were challenging for the women who felt that "MS is the third person in a marriage." Spouses need help to maintain appropriate boundaries. Limitations of the study include the small, economically homogeneous sample and the single encounter with the subjects. A longitudinal intervention study is needed. PMID:15794441

  7. Rodent Models of Amyotrophic Lateral Sclerosis.

    PubMed

    Philips, Thomas; Rothstein, Jeffrey D

    2015-06-01

    Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%). The large majority of fALS cases are due to genetic mutations in the Superoxide dismutase 1 gene (SOD1, 15% of fALS) and repeat nucleotide expansions in the gene encoding C9ORF72 (∼ 40% to 50% of fALS and ∼ 10% of sALS). Studies suggest that ALS is mediated through aberrant protein homeostasis (i.e., ER stress and autophagy) and/or changes in RNA processing (as in all non-SOD1-mediated ALS). In all of these cases, animal models suggest that the disorder is mediated non-cell autonomously, i.e., not only motor neurons are involved, but glial cells including microglia, astrocytes, and oligodendrocytes, and other neuronal subpopulations are also implicated in the pathogenesis. Provided in this unit is a review of ALS rodent models, including discussion of their relative advantages and disadvantages. Emphasis is placed on correlating the model phenotype with the human condition and the utility of the model for defining the disease process. Information is also presented on RNA processing studies in ALS research, with particular emphasis on the newest ALS rodent models.

  8. Pediatric multiple sclerosis: Clinical features and outcome.

    PubMed

    Waldman, Amy; Ness, Jayne; Pohl, Daniela; Simone, Isabella Laura; Anlar, Banu; Amato, Maria Pia; Ghezzi, Angelo

    2016-08-30

    Multiple sclerosis (MS) in children manifests with a relapsing-remitting MS (RRMS) disease course. Acute relapses consist of new neurologic deficits persisting greater than 24 hours, in the absence of intercurrent illness, and occur with a higher frequency early in the disease as compared to adult-onset RRMS. Most pediatric patients with MS recover well from these early relapses, and cumulative physical disability is rare in the first 10 years of disease. Brainstem attacks, poor recovery from a single attack, and a higher frequency of attacks portend a greater likelihood of future disability. Although prospective pediatric-onset MS cohorts have been established in recent years, there remains very limited prospective data detailing the longer-term clinical outcome of pediatric-onset MS into adulthood. Whether the advent of MS therapies, and the largely off-label access to such therapies in pediatric MS, has improved prognosis is unknown. MS onset during the key formative academic years, concurrent with active cognitive maturation, is an important determinant of long-term outcome, and is discussed in detail in another article in this supplement. Finally, increasing recognition of pediatric MS worldwide, recent launch of phase III trials for new agents in the pediatric MS population, and the clear imperative to more fully appreciate health-related quality of life in pediatric MS through adulthood highlight the need for standardized, validated, and robust outcome measures. PMID:27572865

  9. Therapeutic Yoga: Symptom Management for Multiple Sclerosis.

    PubMed

    Rogers, Kim A; MacDonald, Megan

    2015-11-01

    Multiple sclerosis (MS) is the most common autoimmune inflammatory demyelinating disease of the central nervous system, affecting over 2.3 million people worldwide. According to the National Institute of Neurological Disorders and Stroke, the age of disease onset is typically between 20 and 40 years, with a higher incidence in women. Individuals with MS experience a wide range of symptoms, including declining physical, emotional, and psychological symptoms (e.g., fatigue, imbalance, spasticity, chronic pain, cognitive impairment, bladder and bowel dysfunction, visual and speech impairments, depression, sensory disturbance, and mobility impairment). To date, both the cause of and cure for MS remain unknown. In recent years, more individuals with MS have been pursuing alternative methods of treatment to manage symptoms of the disease, including mind-body therapies such as yoga, meditation, breathing, and relaxation techniques. It has been suggested that the practice of yoga may be a safe and effective way of managing symptoms of MS. Therefore, the purpose of this paper is to summarize the most relevant literature on exercise and mind-body modalities to treat MS symptoms and, more specifically, the benefits and potential role of yoga as an alternative treatment of symptom management for individuals with MS. The article also discusses future directions for research. PMID:26270955

  10. [The Multiple Sclerosis Documentation System MSDS. Discussion of a documentation standard for multiple sclerosis].

    PubMed

    Pette, M; Eulitz, M

    2002-02-01

    The MSDS (multiple sclerosis documentation system) has been developed at the Department of Neurology, Technical University of Dresden, Germany, during the last 4 years. The first version of this database application has been in use since October 2000. The MSDS manages information on MS patients, their treating physicians, patient history (symptoms, other diseases, biographical history, family history, habits, medication), clinical signs, results of laboratory examinations (blood chemistry, autoantibodies, borrelia serology, evoked potentials, cranial and spinal cord magnetic resonance imaging), clinical scores relevant for MS, and biosamples. In principle, MSDS allows online data input and semiautomatically generates reports to all general practitioners and neurologists treating the respective patient. Patient information sheets and internal treatment guidelines are part of the system. During a 3-month evaluation, the first version of MSDS was tested at eight university multiple sclerosis ambulatory care units and one general neurology hospital. The overall judgement was favorable. Suggestions for changes and improvements, as well as practical experiences, were considered when developing MSDS 2.0, which will be available by the end of 2001. PMID:11975090

  11. No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

    PubMed Central

    Goris, An; van Setten, Jessica; Diekstra, Frank; Ripke, Stephan; Patsopoulos, Nikolaos A.; Sawcer, Stephen J.; van Es, Michael; Andersen, Peter M.; Melki, Judith; Meininger, Vincent; Hardiman, Orla; Landers, John E.; Brown, Robert H.; Shatunov, Aleksey; Leigh, Nigel; Al-Chalabi, Ammar; Shaw, Christopher E.; Traynor, Bryan J.; Chiò, Adriano; Restagno, Gabriella; Mora, Gabriele; Ophoff, Roel A.; Oksenberg, Jorge R.; Van Damme, Philip; Compston, Alastair; Robberecht, Wim; Dubois, Bénédicte; van den Berg, Leonard H.; De Jager, Philip L.; Veldink, Jan H.; de Bakker, Paul I.W.

    2014-01-01

    Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS. PMID:24234648

  12. Design Documentation for JaWE2Openflow Project

    SciTech Connect

    Mehta, N; Barter, R H

    2004-07-29

    Lawrence Livermore National Laboratory (LLNL) has chosen CIGNEX Technologies, Inc. (CIGNEX) to design and develop the JaWE2Openflow conversion software. This document was created by CIGNEX as a project deliverable.

  13. RuBPCase activase mediates growth-defense tradeoffs: Silencing RCA redirects JA flux from JA-Ile to MeJA to attenuate induced defense responses in Nicotiana attenuata

    PubMed Central

    Mitra, Sirsha; Baldwin, Ian T.

    2014-01-01

    Summary RuBPCase activase (RCA), an abundant photosynthetic protein is strongly down-regulated in response to Manduca sexta’s oral secretion (OS) in Nicotiana attenuata. RCA-silenced plants are impaired not only in photosynthetic capacity and growth, but also in jasmonic acid (JA)-isoleucine (Ile) signaling, and herbivore resistance mediated by JA-Ile dependent defense traits. These responses are consistent with a resource-based growth-defense trade-off. Since JA+Ile-supplementation of OS restored WT levels of JA-Ile, defenses and resistance to M. sexta, but OS supplemented individually with JA- or Ile did not, the JA-Ile deficiency of RCA-silenced plants could not be attributed to lower JA or Ile pools or JAR4/6 conjugating activity. Similar levels of JA-Ile derivatives after OS elicitation indicated unaltered JA-Ile turnover and lower levels of other JA-conjugates ruled out competition from other conjugation reactions. RCA-silenced plants accumulated more methyl jasmonate (MeJA) after OS elicitation, which corresponded with increased jasmonate methyltransferase (JMT) activity. RCA-silencing phenocopies JMT over-expression, wherein elevated JMT activity redirects OS-elicited JA flux towards inactive MeJA, creating a JA sink which depletes JA-Ile and its associated defense responses. Hence RCA plays an additional non-photosynthetic role in attenuating JA-mediated defenses and their associated costs potentially allowing plants to anticipate resource-based constraints on growth before they actually occur. PMID:24491116

  14. Diagnosis and Management of Multiple Sclerosis in Children

    PubMed Central

    NAJAFI, Mohammad Reza; NAJAFI, Mohammad Amin; NASR, Zahra

    2016-01-01

    Growing evidence indicates the safety and well toleration of treatment by Disease-modifying in children suffering multiple sclerosis (MS). The treatment is not straight forward in a great number of patients, thus patients with pediatric MS must be managed by experienced specialized centers. Common treatments of multiple sclerosis for adults are first-line therapies. These therapies (firstline) are safe for children. Failure in treatment that leads to therapy alteration is almost prevalent in pediatric MS. Toleration against current second-line therapies has been shown in multiple sclerosis children. Oral agents have not been assessed in children MS patients. Although clinical trials in children are insufficient, immunomodulating managed children, experience a side effect similar to the adult MS patients. However, further prospective clinical studies, with large sample size and long follow-up are needed to distinguish the benefits and probable side effects of pediatric MS therapies. PMID:27375751

  15. Remyelination strategies in multiple sclerosis: a critical reflection.

    PubMed

    Kipp, Markus

    2016-01-01

    Remyelination is the natural repair mechanism of demyelination and can be a highly efficient process in multiple sclerosis. However, in the majority of lesions, this regenerative approach is incomplete or fails. It is believed that remyelination protects against progressive axonal damage and thus long-term disability in patients with multiple sclerosis. For this reason, therapeutic promotion of remyelination represents an attractive option for preventing disease progression. In this editorial we casts a critical eye over the most frequently used experimental settings which aim to uncover potential remyelination promoting drugs. This article reflects upon the personal opinion of the author who currently used animal models allow to assess the potency of pharmacological interventions to accelerate, but not to induce myelin repair. Furthermore, it is discussed how remyelination and neuroprotection might well be two separate entities. Thus, induction of remyelination does not necessarily prevent disease progression in multiple sclerosis patients. PMID:26618372

  16. Clinically silent seizures in a neonate with tuberous sclerosis.

    PubMed

    Ikeno, Mitsuru; Okumura, Akihisa; Abe, Shinpei; Igarashi, Ayuko; Hisata, Ken; Shoji, Hiromichi; Shimizu, Toshiaki

    2016-01-01

    Although seizures during infancy in patients with tuberous sclerosis complex are common, seizures in neonates are infrequent. Here, we report the clinical course and electroencephalography (EEG) findings of a neonate with tuberous sclerosis complex associated with clinically silent seizures. The patient was a girl in whom cardiac tumors were detected on fetal ultrasonography. Brain magnetic resonance imaging during the neonatal period showed subependymal and cortical tubers. Routine EEG indicated unexpected ictal changes with no noticeable clinical symptoms. Ictal EEG was associated with a subtle increase in heart rate and a brief increase in chin electromyogram. These changes were difficult to identify clinically. The patient later developed focal seizures and epileptic spasms and had severe psychomotor delay. The present case suggests the occurrence of clinically silent seizures before the appearance of epileptic spasms in infants with tuberous sclerosis, and that EEG is an option for neonates with a prenatal diagnosis. PMID:26712128

  17. Renal hamartoma (angiomyolipoma) and the tuberous sclerosis complex.

    PubMed

    Pacis, A B; Norman, C H

    1979-01-01

    Renal hamartoma is found in 40 to 80 percent of patients with tuberous sclerosis. Microscopic demonstration of fat in the tissues of the mass is felt to be the most reliable diagnostic criterion of hamartoma.Characteristically, the angiographic appearance demonstrates a large, dilated feeding vessel passing through the mass with multiple, multisacculated aneurysmal dilatations appearing like bunches of grapes. There is a delicate neovascularity without A-V shunting and an onion-peel or whorl-like appearance in the venous phase.This case is presented to point out the close association of renal hamartoma and tuberous sclerosis and the need to search for renal hamartoma when the diagnosis of tuberous sclerosis is made. PMID:423276

  18. Current management of the gastrointestinal complications of systemic sclerosis.

    PubMed

    Emmanuel, Anton

    2016-08-01

    Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation.

  19. Anti-inflammatory effects of melatonin in multiple sclerosis.

    PubMed

    Farez, Mauricio F; Calandri, Ismael L; Correale, Jorge; Quintana, Francisco J

    2016-10-01

    Melatonin is a hormone with complex roles in the pathogenesis of autoimmune disorders. Over the years, it has become clear that melatonin may exacerbate some autoimmune conditions, whereas it alleviates others such as multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by a dysregulated immune response directed against the central nervous system. Indeed, the balance between pathogenic CD4(+) T cells secreting IFN-γ (TH 1) or IL-17 (TH 17); and FoxP3(+) regulatory T cells and IL-10(+) type 1 regulatory T cells (Tr1 cells) is thought to play an important role in disease activity. Recent evidence suggests that melatonin ameliorates multiple sclerosis by controlling the balance between effector and regulatory cells, suggesting that melatonin-triggered signaling pathways are potential targets for therapeutic intervention. Here, we review the available data on the effects of melatonin on immune processes relevant for MS and discuss its therapeutic potential. PMID:27561251

  20. Role of oral teriflunomide in the management of multiple sclerosis.

    PubMed

    Tanasescu, Radu; Evangelou, Nikos; Constantinescu, Cris S

    2013-01-01

    The landscape of the treatment of relapsing-remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing-remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing-remitting multiple sclerosis is discussed. PMID:23637535

  1. Ammon's horn sclerosis: its pathogenesis and clinical significance.

    PubMed

    Sano, K; Kirino, T

    1990-08-01

    Sclerosis of the cornu Ammonis or Ammon's horn sclerosis (AHS) is an "often-described, yet hitherto enigmatic phenomena" as Spielmyer put it in 1927. It has been found in cases with ischemia, anoxia or hypoglycemia and in more than half of the epileptic brains examined at autopsy. Various theories about its pathogenesis have been propounded. Among them, the "Pathoklise" theory of the Vogts and the vascular theory of Spielmeyer and his associates were prevailing until recently. In 1953, two articles were published to contribute to the pathogenesis of ictal automatism (a type of complex partial or temporal lobe seizures). One is the incisural sclerosis theory by Penfield and his associates and the other is the Ammon's horn sclerosis theory by Sano and Malamud. The former authors described a diffuse sclerosis of the infero-mesial temporal structures without, however, specifically relating it to AHS. They considered it was the result of localized anoxia of that portion of the brain caused by incisural herniation occurring during parturition. Sano and Malamud maintained that AHS is a result of convulsions, a distinct scar adjacent to which epileptogenic foci may develop in the course of time to cause ictal automatism. The latter theory was corroborated by Sano, Falconer and others. Falconer expanded the theory to the assertion that not only ictal automatism but other types of intractable epilepsy may be due to "mesial temporal (Ammon's horn) sclerosis". The most recent development in the pathogenesis of AHS is the excitotoxicity theory. Namely, AHS is caused by excessive excitation of neurons, probably by putative excitatory neurotransmitters, especially, glutamate. For this theory, there is a significant body of evidence. The problem of AHS, an old research subject and a matter of long-lasting controversy, has now been updated and become one of the newest topics in the field of experimental neurobiology.

  2. Disconnection as a mechanism for cognitive dysfunction in multiple sclerosis.

    PubMed

    Dineen, R A; Vilisaar, J; Hlinka, J; Bradshaw, C M; Morgan, P S; Constantinescu, C S; Auer, D P

    2009-01-01

    Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been studied. We apply tract-based spatial statistics (TBSS) to diffusion tensor imaging (DTI) in a cohort of multiple sclerosis patients to identify loci where reduced white matter tract fractional anisotropy (FA) predicts impaired performance in cognitive testing. Thirty-seven multiple sclerosis patients in remission (median age 43.5 years; Expanded Disability Status Scale range 1.5-6.5; 35 relapsing remitting, two secondary-progressive) underwent 3 T MRI including high-resolution DTI. Multiple sclerosis patients underwent formal testing of performance in multiple cognitive domains. Normalized cognitive scores were used for voxel-wise statistical analysis using TBSS, while treating age as a covariate of no interest. Permutation-based inference on cluster size (t > 2, P <0.05 corrected) was used to correct for multiple comparisons. Statistical mapping revealed differential patterns of FA reduction for tests of sustained attention, working memory and processing speed, visual working memory and verbal learning and recall. FA was not associated with frontal lobe function or visuospatial perception. Cognitively relevant tract localizations only partially overlapped with areas of high FLAIR lesion probability, confirming the contribution of normal-appearing white matter abnormality to cognitive dysfunction. Of note, tract localizations showing significant associations with cognitive impairment were found to interconnect cortical regions thought to be involved in processing in these cognitive domains, or involve possible compensatory processing pathways. This suggests that TBSS reveals functionally relevant tract injury underlying

  3. Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

    PubMed

    Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

    2015-06-01

    Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the

  4. Immune Rebound: Multiple Sclerosis after Treatment of Cushing's Disease.

    PubMed

    Soveid, Mahmood; Petramfar, Peyman

    2016-03-01

    High cortisol level in endogenous Cushing's syndrome suppresses the immune system and after treatment there may be an over activity of immune reaction leading to autoimmune diseases mostly thyroid and rheumatologic disorders. This is the second reported case of multiple sclerosis developing after treatment of Cushing's syndrome. A 42-year old man is reported who presented with bone fracture and osteoporosis and diagnosed with Cushing's disease. Six months after surgical treatment of his pituitary adenoma, he developed progressive multiple sclerosis. We conclude that after treatment of endogenous Cushing's syndrome, the patients should be watched for development of autoimmune disorders including those affecting the central nervous system. PMID:27026048

  5. The heart and tuberous sclerosis. An echocardiographic and electrocardiographic study.

    PubMed Central

    Gibbs, J L

    1985-01-01

    Cross sectional echocardiography, 12 lead electrocardiography, and 24 hour ambulatory electrocardiography were performed in eleven patients with tuberous sclerosis. Echocardiography showed single or multiple intramyocardial masses, most commonly in the ventricular septum, suggestive of rhabdomyomata in seven of the eleven cases. One patient with a normal echocardiogram showed ventricular pre-excitation on electrocardiography, with tachycardias of 180 beats per minute on ambulatory monitoring. Sinus bradycardia, sinus tachycardia, and supraventricular tachycardia were also seen, but their importance is uncertain. Echocardiography and electrocardiography should be routinely performed in the assessment of patients with tuberous sclerosis and ambulatory electrocardiography should be considered in those with seizures that respond poorly to anticonvulsants. Images PMID:4074592

  6. Management of Fatigue in Persons with Multiple Sclerosis

    PubMed Central

    Khan, Fary; Amatya, Bhasker; Galea, Mary

    2014-01-01

    Fatigue is one of the most common symptoms of multiple sclerosis. Despite advances in pharmacological and non-pharmacological treatment, fatigue continues to be the disabling symptom in persons with MS (pwMS), affecting almost 80% of pwMS. In current practice, both pharmacological and non-pharmacological interventions are used in combination, encompassing a multi-disciplinary approach. The body of research investigating the effect of these interventions is growing. This review systematically evaluated the existing evidence on the effectiveness and safety of different interventions currently applied for the management of fatigue in person with multiple sclerosis in improving patient outcomes, to guide treating clinicians. PMID:25309504

  7. Treatment of systemic sclerosis: potential role for stem cell transplantation

    PubMed Central

    Xiong, Wen; Derk, Chris T

    2009-01-01

    Hematopoietic stem cell transplantation may “reset” the immune reconstitution and induce self tolerance of autoreactive lymphocytes, and has been explored in the treatments for systemic sclerosis. Phase I/II trials have shown a satisfactory risk benefit ratio. The true benefit will be identified by two ongoing prospective, randomized phase III trials. Multipotent mesenchymal stromal cells (MSCs) possess antiproliferative, anti-inflammatory, and immunosuppressive properties. The use of MSCs has showed successful responses in patients with severe steroid-resistant acute graft versus host disease in phase II trials, and may be a potentially promising option for patients with systemic sclerosis. PMID:24198505

  8. Pulmonary hyalinizing granuloma: an unusual association with multiple sclerosis.

    PubMed

    John, P G; Rahman, J; Payne, C B

    1995-10-01

    Pulmonary hyalinizing granuloma (PHG) is a rare entity included in the differential diagnosis of pulmonary nodules of unknown origin. The pathologic entity may represent a peculiar form of pulmonary immune reaction. We report the case of a 40-year-old white woman who had nodular lesions in both lung bases after a 10-year history of multiple sclerosis. An open lung biopsy was required to make the diagnosis. The association of pulmonary hyalinizing granuloma with multiple sclerosis could be coincidental, but since there is a possibility of immune reaction in the pathogenesis of both diseases, the association may be significant. PMID:7481968

  9. Immune Rebound: Multiple Sclerosis after Treatment of Cushing's Disease.

    PubMed

    Soveid, Mahmood; Petramfar, Peyman

    2016-03-01

    High cortisol level in endogenous Cushing's syndrome suppresses the immune system and after treatment there may be an over activity of immune reaction leading to autoimmune diseases mostly thyroid and rheumatologic disorders. This is the second reported case of multiple sclerosis developing after treatment of Cushing's syndrome. A 42-year old man is reported who presented with bone fracture and osteoporosis and diagnosed with Cushing's disease. Six months after surgical treatment of his pituitary adenoma, he developed progressive multiple sclerosis. We conclude that after treatment of endogenous Cushing's syndrome, the patients should be watched for development of autoimmune disorders including those affecting the central nervous system.

  10. HLA and multiple sclerosis in south east Wales.

    PubMed Central

    Swingler, R J; Kirk, P F; Darke, C; Compston, D A

    1987-01-01

    A stronger association has been found between multiple sclerosis and HLA-DR2 than -DQwl in south east Wales (prevalence c 113/10(5)) in contrast to recent observations in north east Scotland (prevalence 178/10(5). The complex relationship between the HLA system and multiple sclerosis, demonstrated in this and other studies, is explained more easily under a polygenic model of inheritance, in which environmental events and genes interact, than by the presence of a single susceptibility gene. PMID:3499485

  11. Focal stent collapse in a patient with systemic sclerosis.

    PubMed

    Di Francesco, L; Finci, L; Reimers, B; Di Mario, C; Colombo, A

    1998-05-01

    We report a patient with systemic sclerosis having implantation of a 35 mm beStent with immediate success but developing angina at follow-up. A focal stent collapse with focal hyperplasia in and outside the stent was documented by ultrasound after 2 mos. A 14mm Palmaz-Schatz stent was successfully deployed into the collapsed beStent, with good 6-mo angiographic result. The stent collapse was probably due to unequal distribution of radial forces and possibly reactive hyperplasia in this unique patient with systemic sclerosis.

  12. Current management of relapsing-remitting multiple sclerosis.

    PubMed

    Sedal, L; Wilson, I B; McDonald, E A

    2014-10-01

    Multiple sclerosis was without effective disease-modifying therapy for many years. The introduction of the injectable therapies (interferon and glatiramer acetate) some 20 years ago was considered a major advance. Recent years have heralded a revolution in treatment options with the introduction of intravenous natalizumab and, even more recently, three oral agents. We are currently in a period of determining the best use of these therapies to ensure prevention of disease progression while maintaining patient safety. Despite these new treatments, there are still many patients living with disability as a result of multiple sclerosis and significant attention must be given to symptomatic management. PMID:25302718

  13. Neuropathology of Amyotrophic Lateral Sclerosis and Its Variants.

    PubMed

    Saberi, Shahram; Stauffer, Jennifer E; Schulte, Derek J; Ravits, John

    2015-11-01

    The neuropathologic molecular signature common to almost all sporadic amyotrophic lateral sclerosis (ALS) and most familial ALS is TDP-43 immunoreactive neuronal cytoplasmic inclusions. The neuropathologic and molecular neuropathologic features of ALS variants, primarily lateral sclerosis and progressive muscular atrophy, are less certain but also seem to share the primary features of ALS. Genetic causes, including mutations in SOD1, TDP-43, FUS, and C9orf72, all have distinctive molecular neuropathologic signatures. Neuropathology will continue to play an increasingly key role in solving the puzzle of ALS pathogenesis.

  14. Inhibitory dysfunction in amyotrophic lateral sclerosis: future therapeutic opportunities.

    PubMed

    Clark, Rosemary; Blizzard, Catherine; Dickson, Tracey

    2015-12-01

    In amyotrophic lateral sclerosis, motor neuron hyperexcitability and inhibitory dysfunction is emerging as a potential causative link in the dysfunction and degeneration of the motoneuronal circuitry that characterizes the disease. Interneurons, as key regulators of excitability, may mediate much of this imbalance, yet we know little about the way in which inhibitory deficits perturb excitability. In this review, we explore inhibitory control of excitability and the potential contribution of altered inhibition to amyotrophic lateral sclerosis disease processes and vulnerabilities, identifying important windows of therapeutic opportunity and potential interventions, specifically targeting inhibitory control at key disease stages.

  15. Gait variability and disability in multiple sclerosis.

    PubMed

    Socie, Michael J; Motl, Robert W; Pula, John H; Sandroff, Brian M; Sosnoff, Jacob J

    2013-05-01

    Gait variability is clinically relevant in some populations, but there is limited documentation of gait variability in persons with multiple sclerosis (MS). This investigation examined average and variability of spatiotemporal gait parameters in persons with MS and healthy controls and subsequent associations with disability status. 88 individuals with MS (age 52.4±11.1) and 20 healthy controls (age 50.9±8.7) performed two self-paced walking trials on a 7.9-m electronic walkway to determine gait parameters. Disability was indexed by the Expanded Disability Status Scale (EDSS) and ranged between 2.5 and 6.5. Gait variability was indexed by standard deviation (SD) and coefficient of variation (CV=SD/mean) of step time, step length, and step width. Average gait parameters were significantly correlated with EDSS (ρ=0.756-0.609) and were significantly different in individuals with MS compared to controls (p≤0.002). Also, step length (p<0.001) and step time (p<0.001) variability were both significantly greater in MS compared to controls. EDSS was positively correlated with step length variability and individuals with MS who used assistive devices to walk had significantly greater step length variability than those who walked independently (p's<.05). EDSS was correlated with step time and length variability even when age was taken into account. Additionally, Fisher's z test of partial correlations revealed that average gait parameters were more closely related to disability status than gait variability in individuals with MS. This suggests that focusing on average gait parameters may be more important than variability in therapeutic interventions in MS.

  16. The Importance of NAD in Multiple Sclerosis

    PubMed Central

    Penberthy, W. Todd; Tsunoda, Ikuo

    2009-01-01

    The etiology of multiple sclerosis (MS) is unknown but it manifests as a chronic inflammatory demyelinating disease in the central nervous system (CNS). During chronic CNS inflammation, nicotinamide adenine dinucleotide (NAD) concentrations are altered by (T helper) Th1-derived cytokines through the coordinated induction of both indoleamine 2,3-dioxygenase (IDO) and the ADP cyclase CD38 in pathogenic microglia and lymphocytes. While IDO activation may keep auto-reactive T cells in check, hyper-activation of IDO can leave neuronal CNS cells starving for extracellular sources of NAD. Existing data indicate that glia may serve critical functions as an essential supplier of NAD to neurons during times of stress. Administration of pharmacological doses of non-tryptophan NAD precursors ameliorates pathogenesis in animal models of MS. Animal models of MS involve artificially stimulated autoimmune attack of myelin by experimental autoimmune encephalomyelitis (EAE) or by viral-mediated demyelination using Thieler's murine encephalomyelitis virus (TMEV). The WldS mouse dramatically resists razor axotomy mediated axonal degeneration. This resistance is due to increased efficiency of NAD biosynthesis that delays stress-induced depletion of axonal NAD and ATP. Although the WldS genotype protects against EAE pathogenesis, TMEV-mediated pathogenesis is exacerbated. In this review, we contrast the role of NAD in EAE versus TMEV demyelinating pathogenesis to increase our understanding of the pharmacotherapeutic potential of NAD signal transduction pathways. We speculate on the importance of increased SIRT1 activity in both PARP-1 inhibition and the potentially integral role of neuronal CD200 interactions through glial CD200R with induction of IDO in MS pathogenesis. A comprehensive review of immunomodulatory control of NAD biosynthesis and degradation in MS pathogenesis is presented. Distinctive pharmacological approaches designed for NAD-complementation or targeting NAD

  17. Multiple sclerosis: the disease and its manifestations.

    PubMed Central

    McDonald, W I; Ron, M A

    1999-01-01

    Multiple sclerosis is an immune-mediated inflammatory demyelinating disease of the central nervous system clinically characterized by relapses and remissions of neurological disturbance. A typical relapse, exemplified by optic neuritis, increases in severity over a week or two and after approximately one month begins to remit. Resolution takes place over the course of two to three months. In the early stages, clinical recovery is virtually complete, though persistent abnormalities of conduction can usually be detected by evoked potential techniques and persistent structural abnormalities can be detected by magnetic resonance imaging (MRI). These techniques, together with cerebrospinal fluid examination for oligoclonal IgG, provide supporting evidence for the diagnosis which, in the absence of a specific test, nevertheless remains primarily clinical. The course of the disease is very variable, but after a number of years neurological deficit begins to accumulate after each relapse. In most patients, the relapsing and remitting phase of the disease is followed by a phase of continuous progression of disability. Cognitive disturbances can be detected in many patients even quite early in the course of the illness. Deficits in attention, memory and executive skills may be prominent and tend to become increasingly prominent as neurological deficit increases, although this is not always the case. There is some correlation between the extent of MRI abnormalities in the cerebral white matter and the severity of cognitive deficit. Depression and anxiety are commonly experienced but are poorly correlated to the lesion load seen on MRI. In contrast, the much rarer psychotic symptoms, euphoria and emotional lability are closely linked to the severity of white matter disease. PMID:10603614

  18. Pharmacogenomic study in patients with multiple sclerosis

    PubMed Central

    Bustamante, Marta F.; Morcillo-Suárez, Carlos; Malhotra, Sunny; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K.; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio; Sánchez, Antonio J.; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M.; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S.; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier

    2015-01-01

    Objectives: We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). Methods: In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). Results: Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). Conclusions: These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted. PMID:26445728

  19. Fatigue and Comorbidities in Multiple Sclerosis

    PubMed Central

    Fiest, Kirsten M.; Fisk, John D.; Patten, Scott B.; Tremlett, Helen; Wolfson, Christina; Warren, Sharon; McKay, Kyla A.; Berrigan, Lindsay I.

    2016-01-01

    Abstract Background: Fatigue is commonly reported by people with multiple sclerosis (MS). Comorbidity is also common in MS, but its association with the presence of fatigue or fatigue changes over time is poorly understood. Methods: Nine hundred forty-nine people with definite MS were recruited from four Canadian centers. The Fatigue Impact Scale for Daily Use and a validated comorbidity questionnaire were completed at three visits over 2 years. Participants were classified into groups with no fatigue versus any fatigue. Logistic regression was used to determine the relationship between fatigue and each comorbidity at baseline, year 1, year 2, and overall. Results: The incidence of fatigue during the study was 38.8%. The prevalence of fatigue was greater in those who were older (P = .0004), had a longer time since symptom onset (P = .005), and had greater disability (P < .0001). After adjustment, depression (odds ratio [OR], 2.58; 95% confidence interval [CI], 2.03–3.27), irritable bowel syndrome (OR, 1.71; 95% CI, 1.18–2.48), migraine (OR, 1.69; 95% CI, 1.27–2.27), and anxiety (OR, 1.57; 95% CI, 1.15–2.16) were independently associated with fatigue that persisted during the study. There was also an individual-level effect of depression on worsening fatigue (OR, 1.49; 95% CI, 1.08–2.07). Conclusions: Comorbidity is associated with fatigue in MS. Depression is associated with fatigue and with increased risk of worsening fatigue over 2 years. However, other comorbid conditions commonly associated with MS are also associated with persistent fatigue, even after accounting for depression. Further investigation is required to understand the mechanisms by which comorbidities influence fatigue. PMID:27134583

  20. Predictors of Anxiety in Multiple Sclerosis

    PubMed Central

    Hartoonian, Narineh; Terrill, Alexandra L.; Beier, Meghan L.; Turner, Aaron P.; Day, Melissa A.; Alschuler, Kevin N.

    2014-01-01

    Purpose/Objectives The aims of this study were to (1) Identify the predictors of symptoms of anxiety, and (2) Evaluate the differential association of somatic and non-somatic symptoms of depression on anxiety over time in persons with multiple sclerosis (MS). Methods/Design Participants were 513 persons with MS who previously enrolled in a study exploring the experience of living with MS and completed a 4-month follow-up survey. The main outcome measure used was the Hospital Anxiety and Depression Scale-Anxiety (HADS-A). Demographic, disease-associated variables (time since onset of MS, EDSS, pain and fatigue), and time 1 psychological variables (somatic and non-somatic symptoms of depression) were entered into a hierarchical regression model to examine predictors at baseline for anxiety symptoms at time 2. Results Of the 513 participants in this study a large portion of the sample was white (92%), female (82%), and had relapsing-remitting MS (57%). After adjusting for demographic and disease related variables, anxiety (β <.001), employment (β =.07) and non-somatic depressive symptoms (β =.10) at baseline significantly predicted anxiety at time 2, ps<.05. Interactions revealed significant effects for time since onset of MS and somatic symptoms as well as time since onset and non-somatic symptoms, ps<.05. Non-somatic symptoms were more linked to anxiety early in the disease and somatic symptoms were more prominently linked to anxiety later in the disease. Conclusions Findings suggest that non-somatic symptoms of depression and employment predict anxiety in MS. The relationship between different aspects of depression and anxiety may change over the course of the disease. PMID:25496434

  1. Symptomatic therapy and neurorehabilitation in multiple sclerosis.

    PubMed

    Kesselring, Jürg; Beer, Serafin

    2005-10-01

    Multiple sclerosis (MS) is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and handicap. Symptoms that contribute to loss of independence and restrictions in social activities lead to continuing decline in quality of life. Our aim is to give an updated overview on the management of symptoms and rehabilitation measures in MS. Appropriate use of these treatment options might help to reduce long-term consequences of MS in daily life. First, we review treatment of the main symptoms of MS: fatigue, bladder and bowel disturbances, sexual dysfunction, cognitive and affective disorders, and spasticity. Even though these symptomatic therapies have benefits, their use is limited by possible side-effects. Moreover, many common disabling symptoms, such as weakness, are not amenable to drug treatment. However, neurorehabilitation has been shown to ease the burden of these symptoms by improving self-performance and independence. Second, we discuss comprehensive multidisciplinary rehabilitation and specific treatment options. Even though rehabilitation has no direct influence on disease progression, studies to date have shown that this type of intervention improves personal activities and ability to participate in social activities, thereby improving quality of life. Treatment should be adapted depending on: the individual patient's needs, demands of their surrounding environment, type and degree of disability, and treatment goals. Improvement commonly persists for several months beyond the treatment period, mostly as a result of reconditioning and adaptation and appropriate use of medical and social support at home. These findings suggest that quality of life is determined by disability and handicap more than by functional deficits and disease progression. PMID:16168933

  2. Effects of diazoxide in multiple sclerosis

    PubMed Central

    Rovira, Alex; Montalban, Xavier; Arroyo, Rafael; Paul, Friedemann; Meca-Lallana, Virginia; Ramo, Cristina; Fernandez, Oscar; Saiz, Albert; Garcia-Merino, Antonio; Ramió-Torrentà, Lluís; Casanova, Bonaventura; Oreja-Guevara, Celia; Muñoz, Delicias; Martinez-Rodriguez, Jose Enrique; Lensch, Eckart; Prieto, Jose Maria; Meuth, Sven G.; Nuñez, Xavier; Campás, Clara; Pugliese, Marco

    2015-01-01

    Objective: The aim of this study was to test the safety of diazoxide and to search for signs of efficacy in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: In this multicenter, randomized, placebo-controlled, double-blind trial (treatment allocation was concealed), 102 patients with RRMS were randomized to receive a daily oral dose of diazoxide (0.3 and 4 mg/d) or placebo for 24 weeks (NCT01428726). The primary endpoint was the cumulative number of new T1 gadolinium-enhancing lesions per patient, recorded every 4 weeks from week 4 to week 24. Secondary endpoints included brain MRI variables such as the number of new/enlarging T2 lesions and the percentage brain volume change (PBVC); clinical variables such as the percentage of relapse-free patients, relapse rate, and change in the Expanded Disability Status Scale score; and safety and tolerability. Results: Diazoxide was well-tolerated and it produced no serious adverse events other than 1 case of Hashimoto disease. At the 2 doses tested, diazoxide did not improve the primary endpoint or the MRI and clinical variables related to the presence of new lesions or relapses. Patients treated with diazoxide showed reduced PBVC compared with the placebo group, although such changes could be confounded by the higher disease activity of the treated group and the vascular effects of diazoxide. Conclusion: At the doses tested, oral diazoxide did not decrease the appearance of new lesions evident by MRI. The effects in slowing the progression of brain atrophy require further validation. Classification of evidence: This study provides Class I evidence that for patients with RRMS, diazoxide (0.3 and 4 mg/d) does not significantly change the number of new MRI T1 gadolinium-enhancing lesions. PMID:26405686

  3. [Announcement of amyotrophic lateral sclerosis diagnosis].

    PubMed

    Couratier, P; Desport, J C; Torny, F; Lacoste, M

    2006-06-01

    Breaking the news of amyotrophic lateral sclerosis (ALS) is considered as a daunting task in most cases and is not a standardizable procedure. However, proven techniques exist to reduce the trauma to the patient. Announcing ALS falls upen the neurologist who must respect the ethical principle of the patient's independence. After the diagnosis is firmly established, the patient should be informed that he or she has a progressive disease of the motor nerves, for which no curative therapy is available. The name of the disease must be stated and explained. If the family history is negative, it is reassuring for the patient and family to know that their children are unlikely to be at risk. Positive aspects (no pain, no disturbances in sensation, cognition, memory and continence) should be stressed as well as the availability of efficient palliative measures for practically all symptoms. Current research efforts, and when available, the possibility of taking part in clinical studies of new drugs should be pointed out as a means of hope. The answer to the question of prognosis should include the information that there are no sudden worsenings to be expected, that the course of ALS may vary between months and decades, that making a firm statement on prognosis all but impossible for any single patient and that respiratory function may worsen during the disease course. It is therefore mandatory to inform patients and families about the existence of ALS patients'associations. The way the patient is told the diagnosis is of great importance and is considered as a multiple-step procedure. Discussion should take place in a private and quiet room and respect some fundamental objectives such as finding out what the patient already knows or suspects and how much more the patient wants to know, observing and responding to the patient's reactions, reinforcing the information and planning the future. It is proven that communicating the diagnosis of ALS in an empathetic fashion is an

  4. Managed care aspects of managing multiple sclerosis.

    PubMed

    Owens, Gary M

    2013-11-01

    Multiple sclerosis (MS) is a chronic disease of the central nervous system usually diagnosed in the second or third decade of life; MS is more common among women than men by a ratio of 3 to 1. With its relatively early age of onset and symptoms that impair patients' quality of life, MS requires lifelong, dynamic treatment, and places a substantial economic burden on individuals, healthcare systems, and society. The costs associated with providing benefits for MS therapy are growing rapidly and the increasing complexity of the MS market is impacting disease management for payers. Employers are also increasingly aware of the costs associated with MS and are asking health plans to advise on the most appropriate and cost-effective ways to manage both pharmacologic and non-pharmacologic therapies for MS. Health plans, by necessity, must therefore balance appropriate access to treatments for MS with the need to manage rising treatment costs. To meet this goal, payers require population-based solutions, guidelines, and treatment algorithms for the management of MS that can be used in clinical and formulary management decision making in the context of an evolving therapeutic landscape. Further, comparative studies are necessary for payers to determine which agents may work best on a population basis. Due to the current lack of appropriate clinical guidance and insufficient head-to-head data on disease-modifying drugs, strategies for health plans and clinical management have been designed using the best available evidence. Undoubtedly, management of this class will continue to evolve with the launch of newer agents. PMID:24494620

  5. Early- versus Late-Onset Systemic Sclerosis

    PubMed Central

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  6. Three allele combinations associated with Multiple Sclerosis

    PubMed Central

    Favorova, Olga O; Favorov, Alexander V; Boiko, Alexey N; Andreewski, Timofey V; Sudomoina, Marina A; Alekseenkov, Alexey D; Kulakova, Olga G; Gusev, Eugenyi I; Parmigiani, Giovanni; Ochs, Michael F

    2006-01-01

    Background Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles. PMID:16872485

  7. Homozygosity analysis in amyotrophic lateral sclerosis

    PubMed Central

    Mok, Kin; Laaksovirta, Hannu; Tienari, Pentti J; Peuralinna, Terhi; Myllykangas, Liisa; Chiò, Adriano; Traynor, Bryan J; Nalls, Michael A; Gurunlian, Nicole; Shatunov, Aleksey; Restagno, Gabriella; Mora, Gabriele; Nigel Leigh, P; Shaw, Chris E; Morrison, Karen E; Shaw, Pamela J; Al-Chalabi, Ammar; Hardy, John; Orrell, Richard W

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) may appear to be familial or sporadic, with recognised dominant and recessive inheritance in a proportion of cases. Sporadic ALS may be caused by rare homozygous recessive mutations. We studied patients and controls from the UK and a multinational pooled analysis of GWAS data on homozygosity in ALS to determine any potential recessive variant leading to the disease. Six-hundred and twenty ALS and 5169 controls were studied in the UK cohort. A total of 7646 homozygosity segments with length >2 Mb were identified, and 3568 rare segments remained after filtering ‘common' segments. The mean total of the autosomal genome with homozygosity segments was longer in ALS than in controls (unfiltered segments, P=0.05). Two-thousand and seventeen ALS and 6918 controls were studied in the pooled analysis. There were more regions of homozygosity segments per case (P=1 × 10−5), a greater proportion of cases harboured homozygosity (P=2 × 10−5), a longer average length of segment (P=1 × 10−5), a longer total genome coverage (P=1 × 10−5), and a higher rate of these segments overlapped with RefSeq gene regions (P=1 × 10−5), in ALS patients than controls. Positive associations were found in three regions. The most significant was in the chromosome 21 SOD1 region, and also chromosome 1 2.9–4.8 Mb, and chromosome 5 in the 65 Mb region. There are more than twenty potential genes in these regions. These findings point to further possible rare recessive genetic causes of ALS, which are not identified as common variants in GWAS. PMID:23612577

  8. Prevalence of celiac disease in multiple sclerosis

    PubMed Central

    2011-01-01

    Background Celiac disease (CD) is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS) patients and their first-degree relatives. Methods We analyzed the prevalence of serological, histological and genetic CD markers in a series of 72 MS patients and in their 126 first-degree relatives, compared to 123 healthy controls. Results Tissue IgA-anti-transglutaminase-2 antibodies were positive in 7 MS patients (10%), compared to 3 healthy controls (2.4%) (p < 0.05). OR: 5.33 (CI-95%: 1.074-26.425). No differences were found in HLA-DQ2 markers between MS patients (29%) and controls (26%) (NS). We detected mild or moderate villous atrophy (Marsh III type) in duodenal biopsies, in 8 MS patients (11.1%). We also found a high proportion of CD among first-degree relatives: 23/126 (32%). Several associated diseases were detected, mainly dermatitis 41 (57%) and iron deficiency anemia in 28 (39%) MS patients. We also found in them, an increased frequency of circulating auto-antibodies such as anti-TPO in 19 (26%), ANA in 11 (15%) and AMA in 2 (3%). Conclusions We have found an increased prevalence of CD in 8 of the 72 MS patients (11.1%) and also in their first-degree relatives (23/126 [32%]). Therefore, increased efforts aimed at the early detection and dietary treatment of CD, among antibody-positive MS patients, are advisable. PMID:21385364

  9. Renal cell carcinoma in tuberous sclerosis complex.

    PubMed

    Yang, Ping; Cornejo, Kristine M; Sadow, Peter M; Cheng, Liang; Wang, Mingsheng; Xiao, Yu; Jiang, Zhong; Oliva, Esther; Jozwiak, Sergiusz; Nussbaum, Robert L; Feldman, Adam S; Paul, Elahna; Thiele, Elizabeth A; Yu, Jane J; Henske, Elizabeth P; Kwiatkowski, David J; Young, Robert H; Wu, Chin-Lee

    2014-07-01

    Renal cell carcinoma (RCC) occurs in 2% to 4% of patients with tuberous sclerosis complex (TSC). Previous reports have noted a variety of histologic appearances in these cancers, but the full spectrum of morphologic and molecular features has not been fully elucidated. We encountered 46 renal epithelial neoplasms from 19 TSC patients and analyzed their clinical, pathologic, and molecular features, enabling separation of these 46 tumors into 3 groups. The largest subset of tumors (n=24) had a distinct morphologic, immunologic, and molecular profile, including prominent papillary architecture and uniformly deficient succinate dehydrogenase subunit B (SDHB) expression prompting the novel term "TSC-associated papillary RCC (PRCC)." The second group (n=15) were morphologically similar to a hybrid oncocytic/chromophobe tumor (HOCT), whereas the last 7 renal epithelial neoplasms of group 3 remained unclassifiable. The TSC-associated PRCCs had prominent papillary architecture lined by clear cells with delicate eosinophilic cytoplasmic thread-like strands that occasionally appeared more prominent and aggregated to form eosinophilic globules. All 24 (100%) of these tumors were International Society of Urological Pathology (ISUP) nucleolar grade 2 or 3 with mostly basally located nuclei. Tumor cells from 17 of 24 TSC-associated PRCCs showed strong, diffuse labeling for carbonic anhydrase IX (100%), CK7 (94%), vimentin (88%), and CD10 (83%) and were uniformly negative for SDHB, TFE3, and AMACR. Gains of chromosomes 7 and 17 were found in 2 tumors, whereas chromosome 3p deletion and TFE3 translocations were not detected. In this study, we reported a sizable cohort of renal tumors seen in TSC and were able to identify them as different morphotypes, which may help to expand the morphologic spectrum of TSC-associated RCC. PMID:24832166

  10. Advances in the management of multiple sclerosis symptoms: pathophysiology and assessment of spasticity in multiple sclerosis.

    PubMed

    Tintoré, Mar

    2015-01-01

    Spasticity is a prevalent and troublesome symptom for people with multiple sclerosis (MS). Common instruments to measure MS spasticity include the clinician-rated (modified) Ashworth scale and the patient-rated 0-10 spasticity Numerical Rating Scale (NRS). Current opinion is that measurement of MS spasticity should incorporate the patient's perspective. Other instruments to assess spasticity-associated symptoms such as the Penn spasms frequency scale, sleep quality NRS and pain NRS can assist in tracking MS spasticity evolution and inform management choices. Worsening spasticity reduces patient autonomy, impacts negatively on quality of life and increases health resource utilization and costs. Despite the wide range of issues associated with MS spasticity, undertreatment is common and standard treatment options (physiotherapy and classical oral therapies) often fail to provide adequate symptomatic control. PMID:26611266

  11. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  12. Decreased Postural Balance in Multiple Sclerosis Patients with Low Disability

    ERIC Educational Resources Information Center

    Fjeldstad, Cecilie; Pardo, Gabriel; Bemben, Debra; Bemben, Michael

    2011-01-01

    To evaluate balance in women with multiple sclerosis (MS) who have low disability and minimal clinical impairments as measured by the Expanded Disability Status Scale (EDSS), and compare them with healthy age-matched controls. Patients were aged between 18 and 64 years; 67 individuals with MS (mu = 44.0 plus or minus 1.2 years) and 45 healthy…

  13. Polycystic kidney disease in tuberous sclerosis complex: case report.

    PubMed

    Kariuki, N; Karanja, M N; McLigeyo, S O

    1998-10-01

    Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder characterised by seizures, mental retardation, cutaneous lesions and visceral harmatoma. We describe a 4 1/2-year old boy in whom in addition to the commonly described features of TSC, adult-type polycystic kidneys, a scantily reported occurrence, was an associated feature. PMID:10065200

  14. Characteristics of diadochokinesis in Parkinson's Disease and Multiple Sclerosis

    NASA Astrophysics Data System (ADS)

    Tjaden, Kris; Watling, Elizabeth

    2002-05-01

    The current study applies a quantitative, acoustic analysis procedure for the study of rapid syllable productions outlined by Kent and colleagues [R. D. Kent et al., J. Med. Sp. Lang. Path. 7, 83-90 (1999)] to syllables produced by speakers with Parkinson's Disease and Multiple Sclerosis. Neurologically healthy talkers will be studied for comparison purposes. Acoustic measures will be reported for syllable repetitions of /p schwa/, /t schwa/, and /k schwa/. Temporal measures will include syllable duration, syllable rate, and stop gap duration. The energy envelope of syllable repetitions will be quantified using measures of rms amplitude minima and maxima. Acoustic measures will be contrasted to determine the extent to which acoustic profiles of diadochokinesis distinguish hypokinetic dysarthria associated with Parkinson's Disease, ataxic dysarthria secondary to Multiple Sclerosis, and spastic dysarthria secondary to Multiple Sclerosis. It also is of interest to determine whether speakers with Parkinson's Disease and Multiple Sclerosis judged to be nondysarthric via perceptual analyses also demonstrate objective, acoustic profiles of diadochokinesis that are within normal limits. [Work supported by NIH.

  15. Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis

    PubMed Central

    Motta, Caterina; Palermo, Eduardo; Studer, Valeria; Germanotta, Marco; Germani, Giorgio; Centonze, Diego; Cappa, Paolo

    2016-01-01

    Background The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. Objective To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. Methods A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. Results We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. Conclusions Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. PMID:26863109

  16. Autism and the Cerebellum: Evidence from Tuberous Sclerosis.

    ERIC Educational Resources Information Center

    Weber, Anna M.; Egelhoff, John C.; McKellop, J. Mark; Franz, David Neal

    2000-01-01

    A study examined the relationship between neuroimaging findings and the behavioral characteristics of 29 patients with tuberous sclerosis. Findings indicate a positive linear relationship between a patient's total number of tubers and degree of intellectual impairment. The number of tubers in the cerebellum was associated with more autistic…

  17. Evaluating Functional Decline in Patients with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Rosenblum, Sara; Weiss, Patrice L.

    2010-01-01

    Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional status. The aim of the study was to examine the added value of simultaneously evaluating fatigue, personal ADL and handwriting performance as indicators for functional decline among patients with MS. Participants were 50 outpatients with MS and 26 matched healthy…

  18. Determinants of Employment Status among People with Multiple Sclerosis.

    ERIC Educational Resources Information Center

    Roessler, Richard T.; Fitzgerald, Shawn M.; Rumrill, Phillip D.; Koch, Lynn C.

    2001-01-01

    Identifies factors predicting employment or lack thereof among adults with multiple sclerosis (MS). Results included the following variables as the best predictors of employment: symptom persistence, severity of symptoms, educational attainment, and presence of cognitive limitations. The relevance of the findings for rehabilitation assessment and…

  19. Bone end sclerosis in renal osteodystrophy simulating osteonecrosis

    SciTech Connect

    Van Lewis, L.; Keats, T.E.

    1982-08-01

    Osteosclerosis of the bone ends is an unusual manifestation of renal osteodystrophy. In evaluating this finding one should be careful to exclude clinical and radiographic evidence for osteonecrosis. In the two known cases of this entity, bone end sclerosis has been found to develop over one to two years with symmetrical involvement of multiple bones.

  20. Predictors of Employment Status for People with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Roessler, Richard T.; Rumrill, Phillip D.; Fitzgerald, Shawn M.

    2004-01-01

    This study examined the relevance of the disease-and-demographics model for explaining the employment outcomes of adults with multiple sclerosis (MS). Participating in a national survey of their employment concerns, 1,310 adults with MS provided data for the study (274 men, 21%; 1,020 women, 78%; 16 participants did not identify their gender).…

  1. From etiology and pathogenesis to therapy of multiple sclerosis.

    PubMed

    Cazzullo, C L

    1978-01-31

    The Author describes the histopathologic picture of the Multiple Sclerosis and Experimental Allergic Encephalitis and discusses some etiopathogenetic hypotheses elaborating on the immunogenetic and immunopathological aspects. The therapeutical problem is analyzed in all its various facets: cortisone derivatives, immunosuppressive products and reabilitation therapy aiming simultaneously at motion reeducation and at individual and group psycotherapy.

  2. Spatiotemporal Coupling of the Tongue in Amyotrophic Lateral Sclerosis

    ERIC Educational Resources Information Center

    Kuruvilla, Mili S.; Green, Jordan R.; Yunusova, Yana; Hanford, Kathy

    2012-01-01

    Purpose: The primary aim of the investigation was to identify deficits in spatiotemporal coupling between tongue regions in amyotrophic lateral sclerosis (ALS). The relations between disease-related changes in tongue movement patterns and speech intelligibility were also determined. Methods: The authors recorded word productions from 11…

  3. Exercise and Quality of Life in Women with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Giacobbi, Peter R., Jr.; Dietrich, Frederick; Larson, Rebecca; White, Lesley J.

    2012-01-01

    The purpose of this study was to evaluate perceptions of quality of life after a 4-month progressive resistance training program for individuals with multiple sclerosis (MS). A second purpose was to examine participants' views about factors that facilitated or impeded exercise behavior. Qualitative interviews were conducted with eight females…

  4. The mystery of the origin of multiple sclerosis.

    PubMed Central

    McDonald, W I

    1986-01-01

    Our present understanding of the aetiology and pathogenesis of multiple sclerosis is discussed in relation to the views of Sir William Gowers. He perceived that both environmental and genetic factors might be implicated in the aetiology of the disease. Evidence for the former was first reported in 1903, but has become convincing only in the past 20 years; the nature of the environmental factor remains obscure. Evidence for a genetic influence on susceptibility has accumulated since the 1930s, the most compelling coming from the recent Canadian twin study. The number and mode of operation of the genetic factors is still uncertain, but there is evidence for the implication of genetically controlled cellular immune mechanisms in the pathogenesis of the disease. The precise relationship between transient changes in immunological status and the development of new lesions has yet to be defined; magnetic resonance imaging (MRI) promises to play a significant role in this analysis because of its sensitivity in detecting abnormalities in multiple sclerosis. MRI is not in itself specific; it is probable that the similar appearances in multiple sclerosis and cerebral vascular disease both derive at least in part from the influence of astrocytic gliosis on proton content and distribution. The significance of the gliosis is uncertain. Gowers believed that the primary defect in multiple sclerosis lay in the astrocyte. Recent observations on the immunological functions of this cell in vitro suggest that it could be involved early in the pathogenesis of the lesion. Images PMID:2936869

  5. Systemic sclerosis: a rare cause of heart failure?

    PubMed

    González-Cambeiro, María Cristina; Abu-Assi, Emad; Abumuaileq, Rami Riziq-Yousef; Raposeiras-Roubín, Sergio; Rigueiro-Veloso, Pedro; Virgós-Lamela, Alejandro; Díaz-Castro, Oscar; González-Juanatey, José Ramón

    2015-10-01

    Systemic sclerosis (SS) is a chronic disease in which there may be multisystem involvement. It is rare (estimated prevalence: 0.5-2/10000) with high morbidity and mortality, and there is as yet no curative treatment. We report the case of a young woman newly diagnosed with SS, in whom decompensated heart failure was the main manifestation.

  6. A regenerative approach to the treatment of multiple sclerosis

    PubMed Central

    Deshmukh, Vishal A.; Tardif, Virginie; Lyssiotis, Costas A.; Green, Chelsea C.; Kerman, Bilal; Kim, Hyung Joon; Padmanabhan, Krishnan; Swoboda, Jonathan G.; Ahmad, Insha; Kondo, Toru; Gage, Fred H.; Theofilopoulos, Argyrios N.

    2015-01-01

    Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches. PMID:24107995

  7. A perspective on stem cell modeling of amyotrophic lateral sclerosis.

    PubMed

    de Boer, A Sophie; Eggan, Kevin

    2015-01-01

    Amyotrophic lateral sclerosis is a complex neurodegenerative disease. Limitations in animal models have impeded progress in studying disease pathology and potential drug discovery. Here, we will review recent advances in the development of stem cell models for the study of ALS. Additionally, we will discuss the progress toward therapeutic development derived from these stem cell based assays.

  8. Fluvoxamine treatment of major depression associated with multiple sclerosis.

    PubMed

    Benedetti, Francesco; Campori, Euridice; Colombo, Cristina; Smeraldi, Enrico

    2004-01-01

    Fluvoxamine 200 mg was administered for 3 months to a group of 43 interferon beta-1b treated patients affected by major depression associated with multiple sclerosis. Despite a 16.3% attrition rate, 79% of patients achieved response. The drug was well tolerated.

  9. Amyotrophic Lateral Sclerosis: An Introduction to Psychosocial and Behavioral Adaptations.

    ERIC Educational Resources Information Center

    Hoffman, R. Leigh; Decker, Thomas W.

    1993-01-01

    Defines amyotrophic lateral sclerosis (ALS) as motor-neuron disease that is terminal. Discusses symptoms associated with ALS and identifies treatment options. Reviews psychological and behavioral adaptations in regard to ALS clients, their families, and professionals who work with them. Discusses support groups as method of reducing stress for ALS…

  10. Amyotrophic Lateral Sclerosis Patients' Perspectives on Use of Mechanical Ventilation.

    ERIC Educational Resources Information Center

    Young, Jenny M.; And Others

    1994-01-01

    Interviewed 13 amyotrophic lateral sclerosis patients. All believed that they alone should make decision regarding use of mechanical ventilation. Factors they considered important were quality of life, severity of disability, availability of ventilation by means of nasal mask, possible admission to long-term care facility, ability to discontinue…

  11. Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany.

    PubMed

    Wolf, Joachim; Wöhrle, Johannes C; Palm, Frederick; Nix, Wilfred A; Maschke, Matthias; Safer, Anton; Becher, Heiko; Grau, Armin J

    2014-06-01

    There is a lack of prospective and population based epidemiological data on amyotrophic lateral sclerosis in Germany to date. The ALS registry Rhineland-Palatinate was established to investigate the incidence, course and phenotypic variety of ALS in this south-west German state of about 4 million inhabitants. During the period 2010-2011, consecutive incident patients with amyotrophic lateral sclerosis according to the revised El Escorial criteria were included and followed up using multiple overlapping sources of case ascertainment. One hundred and forty-six patients were enrolled. The annual crude incidence for amyotrophic lateral sclerosis in Rhineland-Palatinate was 1.8/100,000 person-years (95% CI 1.6-2.2). Male to female ratio was 1.1:1. Incidence increased with age reaching a peak in the 70-74 years age group and declined thereafter. Late-onset ALS (≥ 75 years) was found in 14.4% of patients. About 32% of patients presented with bulbar onset. In conclusion, incidence rate of amyotrophic lateral sclerosis in Rhineland-Palatinate is within the range of other prospective population based registers in Europe and North America. Gender ratio is nearly balanced.

  12. Defining reliable disability outcomes in multiple sclerosis.

    PubMed

    Kalincik, Tomas; Cutter, Gary; Spelman, Tim; Jokubaitis, Vilija; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, Francois; Grammond, Pierre; Hupperts, Raymond; Oreja-Guevara, Celia; Boz, Cavit; Pucci, Eugenio; Bergamaschi, Roberto; Lechner-Scott, Jeannette; Alroughani, Raed; Van Pesch, Vincent; Iuliano, Gerardo; Fernandez-Bolaños, Ricardo; Ramo, Cristina; Terzi, Murat; Slee, Mark; Spitaleri, Daniele; Verheul, Freek; Cristiano, Edgardo; Sánchez-Menoyo, José Luis; Fiol, Marcela; Gray, Orla; Cabrera-Gomez, Jose Antonio; Barnett, Michael; Butzkueven, Helmut

    2015-11-01

    Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common

  13. Defining reliable disability outcomes in multiple sclerosis.

    PubMed

    Kalincik, Tomas; Cutter, Gary; Spelman, Tim; Jokubaitis, Vilija; Havrdova, Eva; Horakova, Dana; Trojano, Maria; Izquierdo, Guillermo; Girard, Marc; Duquette, Pierre; Prat, Alexandre; Lugaresi, Alessandra; Grand'Maison, Francois; Grammond, Pierre; Hupperts, Raymond; Oreja-Guevara, Celia; Boz, Cavit; Pucci, Eugenio; Bergamaschi, Roberto; Lechner-Scott, Jeannette; Alroughani, Raed; Van Pesch, Vincent; Iuliano, Gerardo; Fernandez-Bolaños, Ricardo; Ramo, Cristina; Terzi, Murat; Slee, Mark; Spitaleri, Daniele; Verheul, Freek; Cristiano, Edgardo; Sánchez-Menoyo, José Luis; Fiol, Marcela; Gray, Orla; Cabrera-Gomez, Jose Antonio; Barnett, Michael; Butzkueven, Helmut

    2015-11-01

    Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common

  14. [Announcement of amyotrophic lateral sclerosis diagnosis].

    PubMed

    Couratier, P; Desport, J C; Torny, F; Lacoste, M

    2006-06-01

    Breaking the news of amyotrophic lateral sclerosis (ALS) is considered as a daunting task in most cases and is not a standardizable procedure. However, proven techniques exist to reduce the trauma to the patient. Announcing ALS falls upen the neurologist who must respect the ethical principle of the patient's independence. After the diagnosis is firmly established, the patient should be informed that he or she has a progressive disease of the motor nerves, for which no curative therapy is available. The name of the disease must be stated and explained. If the family history is negative, it is reassuring for the patient and family to know that their children are unlikely to be at risk. Positive aspects (no pain, no disturbances in sensation, cognition, memory and continence) should be stressed as well as the availability of efficient palliative measures for practically all symptoms. Current research efforts, and when available, the possibility of taking part in clinical studies of new drugs should be pointed out as a means of hope. The answer to the question of prognosis should include the information that there are no sudden worsenings to be expected, that the course of ALS may vary between months and decades, that making a firm statement on prognosis all but impossible for any single patient and that respiratory function may worsen during the disease course. It is therefore mandatory to inform patients and families about the existence of ALS patients'associations. The way the patient is told the diagnosis is of great importance and is considered as a multiple-step procedure. Discussion should take place in a private and quiet room and respect some fundamental objectives such as finding out what the patient already knows or suspects and how much more the patient wants to know, observing and responding to the patient's reactions, reinforcing the information and planning the future. It is proven that communicating the diagnosis of ALS in an empathetic fashion is an

  15. [Cost of multiple sclerosis in France].

    PubMed

    Fromont, A; Lehanneur, M-N; Rollot, F; Weill, A; Clerc, L; Bonithon Kopp, C; Binquet, C; Moreau, T

    2014-01-01

    Multiple sclerosis (MS) is one of the 30 chronic conditions specifically listed by the French healthcare system as a long-term disease (affections de longue durée [ALD]) for which the main health insurance fund (Caisse nationale d'assurance maladie des travailleurs salariés [CNAMTS]) provides full (100%) coverage of healthcare costs. The CNAMTS insures 87% of the French population (52,359,912 of the 60,028,292 inhabitants). The objectives of this study were to evaluate the direct and indirect medical costs of MS among the entire population insured by the CNAMTS in France in 2004. The CNAMTS provided us with access to the ALD database of patients with MS that contains different MS-related expenditures made in 2004. We calculated the overall direct and indirect cost of MS and the cost per patient and per item of expenditure. In 2004, 49,413 patients were registered on the ALD list for MS. Direct cost for MS patients was 469,719,967 €. The direct cost per patient and per year was 9,506 € with variations between regions (French administrative divisions) ranging from 10,800 € in northeastern France (Champagne-Ardenne) to 8,217 € in western France (Pays de la Loire). The different items of expenditure were treatments (44.5%), hospitalization (27.9%), nursing care (5.8%), physiotherapy (5.7%), transport (4%), biology (1.1%), and other (1.5%). During the course of the disease, the overall cost of MS increased slowly during the first 15 years (from 8,000 to 11,000 €), but dramatically the last year of life (23,410 €). The costs of immunomodulator treatments were higher during the first six years after registration on the ALD list. Conversely, physiotherapy costs increased linearly with time during the course of MS. Indirect costs were an estimated 116 million euros in 2004. A disability pension (8,918 € per patient) was perceived by 9,430 patients (19.1%) and a daily allowance (3,317 € per patient) by 9,894 patients (20%). In France, MS has an important

  16. Evolving expectations around early management of multiple sclerosis

    PubMed Central

    Gold, Ralf; Wolinsky, Jerry S.; Amato, Maria Pia; Comi, Giancarlo

    2010-01-01

    Multiple sclerosis is a progressive inflammatory disease of the central nervous system. With prevention or at least delay of disease progression as a key target in the management of multiple sclerosis, current opinion on treatment encourages early intervention with well-tolerated disease-modifying treatments in order to optimize long-term clinical outcomes. Patients presenting with a clinically isolated syndrome (CIS) may progress to clinically definite multiple sclerosis, and clinical trials have demonstrated that early treatment with interferon beta can reduce the conversion rate. Cognitive impairment may already be present in patients with CISs. Today there is evolving evidence that cognitive impairment may be relevant for prognosis and that early treatment with interferon beta may also have a protective effect on the cognitive function. As an accumulation of neuronal loss is now considered to underlie the development of persistent disability in multiple sclerosis, it is crucial that treatment can protect against neuronal damage. In addition to its anti-inflammatory activity, interferon beta may have direct and indirect neuroprotective effects, and several studies have explored the role of interferon beta in regulating neuroprotective factors. With over 15 years of clinical experience as evidence, the long-term safety and efficacy of interferon beta treatment is unquestionable. Results from the CIS studies have demonstrated the high percentage of patients converting to clinically definite multiple sclerosis without treatment and the short- and long-term benefits of an early use of disease-modifying treatments. These findings support starting disease-modifying treatment as soon as the diagnosis of MS is reasonably formulated. PMID:21179596

  17. Multiple sclerosis in malaysia: demographics, clinical features, and neuroimaging characteristics.

    PubMed

    Viswanathan, S; Rose, N; Masita, A; Dhaliwal, J S; Puvanarajah, S D; Rafia, M H; Muda, S

    2013-01-01

    Background. Multiple sclerosis (MS) is an uncommon disease in multiracial Malaysia. Diagnosing patients with idiopathic inflammatory demyelinating diseases has been greatly aided by the evolution in diagnostic criterion, the identification of new biomarkers, and improved accessibility to neuroimaging in the country. Objectives. To investigate the spectrum of multiple sclerosis in Malaysia. Methods. Retrospective analysis with longitudinal follow-up of patients referred to a single tertiary medical center with neurology services in Malaysia. Results. Out of 245 patients with idiopathic inflammatory demyelinating disease, 104 patients had multiple sclerosis. Female to male ratio was 5 : 1. Mean age at onset was 28.6 ± 9.9 years. The Malays were the predominant racial group affected followed by the Chinese, Indians, and other indigenous groups. Subgroup analysis revealed more Chinese having neuromyelitis optica and its spectrum disorders rather than multiple sclerosis. Positive family history was reported in 5%. Optic neuritis and myelitis were the commonest presentations at onset of disease, and relapsing remitting course was the commonest disease pattern observed. Oligoclonal band positivity was 57.6%. At disease onset, 61.5% and 66.4% fulfilled the 2005 and 2010 McDonald's criteria for dissemination in space. Mean cord lesion length was 1.86 ± 1.65 vertebral segments in the relapsing remitting group as opposed to 6.25 ± 5.18 vertebral segments in patients with neuromyelitis optica and its spectrum disorders. Conclusion. The spectrum of multiple sclerosis in Malaysia has changed over the years. Further advancement in diagnostic criteria will no doubt continue to contribute to the evolution of this disease here. PMID:24455266

  18. Salt and Pepper Pigmentation - Skin Manifestation of Systemic Sclerosis.

    PubMed

    Vijayaraju, D; Prakash, G; Yoganandh, T; Subramanian, S R; Ramkumar, S

    2015-09-01

    A 50 year old male presented with progressive difficulty in swallowing both liquid and solid food with no history of Raynaud's phenomenon. A general examination revealed skin changes in the form of thickening, hyperpigmentation and tightening of skin of fingers, hand, forearm and legs. The patient had painless skin induration over the legs, forearm and hand. Salt and pepper pigmentation was seen on the upper back (Figure 1a), over mastoid process (Figure 1b) and the concha of pinna (Figure 1c). Anti-Scl 70 was positive. Anti-centromere antibodies were negative. Pulmonary function testing (PFT) revealed very severe restrictive lung disease. Barium swallow study was normal. Despite being advised to undergo oesophageal manometry test in view of dysphagia, patient was not willing for the same. Diagnosis of systemic sclerosis was made. Systemic sclerosis is a disease in which extensive fibrosis, vascular alterations and autoantibodies against various cellular antigens being the principal features with a female to male ratio of 4:1. Skin pigmentation changes among other features of skin involvement include a salt-and-pepper appearance due to diffuse hyperpigmentation with sparing of the perifollicular areas. This may be due to the richer capillary network that may warm the perifollicular skin and preserve melanogenesis producing the perifollicular pigment retention in systemic sclerosis.1,2 Both cellular and humoral immune factors in combination with external factors such as trauma or inflammation may trigger the destruction of melanocytes.3 Moreover, various physical factors like temperature changes as well as genetic, hormonal factors may influence pigment formation. Such changes in pigmentation is also seen during repigmentation around hair follicles in vitiligo. Clinically, both vitiligo and depigmented lesions of systemic sclerosis present as chalk-white macules with well-defined borders. However, mucosal involvement is commonly seen in vitiligo while depigmented

  19. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    PubMed

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.

  20. Psychopathology in Tuberous Sclerosis: An Overview and Findings in a Population-Based Sample of Adults with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Raznahan, A.; Joinson, C.; O'Callaghan, F.; Osborne, J. P.; Bolton, P. F.

    2006-01-01

    Background: Tuberous sclerosis (TS) is a multi- system disorder with complex genetics. The neurodevelopmental manifestations of TS are responsible for considerable morbidity. The prevalence of epilepsy and intellectual disabilities among individuals with TS have been well described. Ours is the first study that explores the prevalence and pattern…

  1. Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines.

    PubMed

    Gold, Ralf; Oreja-Guevara, Celia

    2013-12-01

    Symptomatic therapy of multiple sclerosis (MS) is an important part of a comprehensive treatment plan that aims to improve patients' quality of life. In the current era of medical progress, several factors have led to the development of guidelines for MS management. There is continued need for an evidence-based approach supported by high-quality data from controlled clinical trials. Most healthcare systems require this approach and include it in the reimbursement process. Guidelines are usually committed by national or continental neurological societies. The Spanish Society of Neurology demyelinating diseases working group has developed a consensus document on spasticity in patients with MS. MS experts from the group used the metaplan method to sum up the most important recommendations about spasticity for inclusion in the guidance. Recommendations were classified according to the Scottish Intercollegiate Guidelines Network system and approved by all members of the group. In Germany, the guideline panel of the German Neurological Society endorsed the national competence network for multiple sclerosis (Krankheitsbezogenes Kompetenznetz Multiple Sklerose) to update the existing recommendations. The most recent fifth edition of the guidelines (dated April 2012) now also includes recommendations for treatment of key symptoms such as spasticity. More than 30 MS neurologists contributed to the new edition reflecting the need for broad expertise. After a first round in which key topics were defined, a web-based decision process was undertaken to further develop individual topics such as symptomatic therapy. The draft manuscript was reviewed once again by the group prior to submission to the official review process. The aims of spasticity treatment are to improve mobility and dexterity, achieve physiological movement patterns, reduce pain, facilitate nursing measures and avoid complications such as contractures. Representative antispasticity medications include baclofen

  2. Sporadic Parkinson disease and amyotrophic lateral sclerosis complex (Brait-Fahn-Schwartz disease).

    PubMed

    Manno, Concetta; Lipari, Alessio; Bono, Valeria; Taiello, Alfonsa Claudia; La Bella, Vincenzo

    2013-03-15

    Clinical evidence for parkinsonism may accompany Amyotrophic Lateral Sclerosis with a frequency ranging from 5% to 17%. The concurrence of Amyotrophic Lateral Sclerosis and Parkinson's disease, outside the known Guam and Kii Peninsula foci, is instead rare, but this raises the possibility of a common pathogenesis. Clinically this complex presents with a levodopa-responsive parkinsonism and Amyotrophic Lateral Sclerosis and has been termed Brait-Fahn-Schwartz disease. Here we describe two patients with this uncommon neurodegenerative complex. Both presented with Parkinson disease and progressed to a full blown Amyotrophic Lateral Sclerosis. We further suggest that the association of Parkinson disease and Amyotrophic Lateral Sclerosis represents a distinct nosological entity, which should be kept separated from extrapyramidal signs and symptoms that may occur in Amyotrophic Lateral Sclerosis.

  3. Drugs in development for relapsing multiple sclerosis.

    PubMed

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral

  4. Drugs in development for relapsing multiple sclerosis.

    PubMed

    Ali, Rehiana; Nicholas, Richard St John; Muraro, Paolo Antonio

    2013-05-01

    Drug development for multiple sclerosis (MS), as with any other neurological disease, faces numerous challenges, with many drugs failing at various stages of development. The disease-modifying therapies (DMTs) first introduced for MS are only moderately effective, but given the lack of competition, they have been widely accepted in clinical practice. Although safety and efficacy continue to be the two main metrics by which drugs will be judged, the newer agents in the market also face challenges of a more comparative nature-are they more efficacious than the currently available drugs on the market? Are they safer or better tolerated? Do they offer any practical advantages over current treatments? Fingolimod represented a milestone following its approval as an oral drug for MS in 2010, offering patients a far more convenient administration route. However, association with cardiovascular complications has led to a more cautious approach in its initial prescribing, now requiring cardiac monitoring for the first 6 h as well as subsequent monitoring of blood pressure and for macular oedema. Natalizumab, amongst licensed drugs, represents the current benchmark for efficacy. The risk of progressive multifocal leukoencephalopathy during natalizumab treatment is now more quantifiable. Other monoclonal antibodies are in various phases of development. Marketing authorisation for alemtuzumab has been filed, and whilst trial data suggest that its efficacy outperforms both licensed drugs and others in development, there is a significant risk of secondary autoimmunity. Its once-yearly administration, however, seems particularly advantageous. Rituximab is unlikely to be developed further as its license will expire, but ocrelizumab, another monoclonal antibody directly targeting B cells, is currently in phase 2 development and looks promising. Daclizumab is also moderately efficacious but may struggle to establish itself given its monthly subcutaneous dosing. There are new oral

  5. Systemic sclerosis associated with cutaneous exposure to solvent: case report and review of the literature

    SciTech Connect

    Brasington, R.D. Jr.; Thorpe-Swenson, A.J. )

    1991-05-01

    Sclerodermatous skin changes and systemic sclerosis have been reported to occur as a result of contact with several different organic solvents. We describe a 41-year-old man who developed systemic sclerosis after working for 15 years in a foundry, where he had extensive cutaneous contact with multiple organic solvents (trichloroethane, xylene, trimethylbenzene, and naphthalene). Cutaneous exposure to organic solvents may be a factor in the etiology of some cases of systemic sclerosis.15 references.

  6. Gastric antral vascular ectasia--a cause of refractory anaemia in systemic sclerosis.

    PubMed

    Busteed, S; Silke, C; Molloy, C; Murphy, M; Molloy, M G

    2001-01-01

    Recurrent gastrointestinal haemorrhage is an uncommon manifestation of systemic sclerosis. We report a case of gastrointestinal bleeding due to gastric antral vascular ectasia (GAVE) in a patient with systemic sclerosis. Failure to recognise the condition as a cause of gastrointestinal bleeding may delay the instigation of appropriate treatment. GAVE should be considered in the differential diagnosis of anaemia in patients with autoimmune conditions such as systemic sclerosis and primary biliary cirrhosis. PMID:11837631

  7. VHA Multiple Sclerosis Surveillance Registry and its similarities to other contemporary multiple sclerosis cohorts.

    PubMed

    Culpepper, William J; Wallin, Mitchell T; Magder, Laurence S; Perencevich, Eli; Royal, Walter; Bradham, Douglas D; Cutter, Gary; Bever, Christopher T

    2015-01-01

    The Veterans Health Administration (VHA) has provided important contributions to our understanding of multiple sclerosis (MS); however, the characteristics of the modern VHA MS population have not been adequately characterized. Our objectives were to compare and contrast characteristics of the VHA MS population with other contemporary MS cohorts. A cross-sectional, mail-based survey of a stratified, random sample of 3,905 VHA users with MS was conducted. Detailed demographic and clinical data were collected as well as patient-reported outcomes assessing disability and quality of life. A total of 1,379 Veterans were enrolled into the MS Surveillance Registry (MSSR). Respondents did not differ from nonrespondents with regard to demographics or region. When compared to several other contemporary MS cohorts, some demographic differences were noted; however, the age of MS onset and diagnosis, subtype distribution, and most prevalent symptoms were very similar across MS cohorts. The MSSR appears to be representative of the general MS population. Combining the extensive VHA health services encounter data with the MSSR provides a rich and unique cohort for study. PMID:26220064

  8. Economic burden of multiple sclerosis and the role of managed sare organizations in multiple sclerosis management.

    PubMed

    Owens, Gary M

    2016-06-01

    Multiple sclerosis (MS) is disease that has an early age of onset and may intensify and subside with disease relapses or exacerbations interrupted by periods of stability. Because of this, patients, their families and caregivers, employers, and the entire healthcare system carry substantial clinical and economic burdens associated with the disease over of a period of many years. Although most patients with MS are covered by health insurance, the management landscape has become increasingly complex over the past decade with the introduction and approval of several new disease-modifying therapies that, while remarkably effective and well tolerated, usually come with a very high cost. Whereas the main goal of treating patients with MS is to prevent disease progression and disability, healthcare and benefit providers are faced with an ever-tipping balance point between effectively managing the disease and maximizing the value of high-cost disease-modifying therapies in an already overburdened healthcare system. Treatment of MS should be individualized, and shared decision making between patients and healthcare providers must be preserved. Healthcare providers and payers need to collaborate to ensure that resources are used optimally and not wasted, reducing both the clinical and economic burdens related to this complex chronic disorder. PMID:27356024

  9. Early-Onset Multiple Sclerosis in Isfahan, Iran: Report of the Demographic and Clinical Features of 221 Patients.

    PubMed

    Etemadifar, Masoud; Nourian, Sayed-Mohammadamin; Nourian, Niloofaralsadat; Abtahi, Seyed-Hossein; Sayahi, Farnaz; Saraf, Zahra; Fereidan-Esfahani, Mahboobeh

    2016-06-01

    It is estimated that early-onset multiple sclerosis multiple sclerosis (early-onset multiple sclerosis) approximately incorporates 3-5% of the multiple sclerosis population. In this report on early-onset multiple sclerosis, the authors aimed to define demographic, clinical and imaging features in a case-series of true-childhood multiple sclerosis and to compare its characteristics with juvenile multiple sclerosis. The authors inspected the records of multiple sclerosis patients who were registered by Isfahan MS Society. Clinical and demographic data of children with less than 16 years of age were reviewed retrospectively. Out of 4536 multiple sclerosis patients referred to the authors' center, 221 patients (4.8%) had multiple sclerosis starting at the age of 16 or less (11 true-childhood multiple sclerosis vs 210 juvenile-onset multiple sclerosis); the female to male ratio was 4.81:1. In the mean follow-up period of 6.2 years, 22 patients (10.5%) had positive family history of multiple sclerosis, 196 (88.6%) patients were classified as relapsing-remitting multiple sclerosis, the mean (± SD Expanded Disability Status Scale) was 1.5 ± 1.1 at the last evaluation. The most common initial presentation was optic nerve involvement (36.1%) and cerebellar sign and symptoms (14.6%). In all, 13 patients (5.8%) had experienced seizure in the course of multiple sclerosis. This study indicated that early-onset multiple sclerosis is not rare condition and overwhelmingly affects girls even at prepubertal onset. Physicians should consider multiple sclerosis in suspicious pediatric cases.

  10. Trigeminal root entry zone involvement in neuromyelitis optica and multiple sclerosis.

    PubMed

    Sugiyama, Atsuhiko; Mori, Masahiro; Masuda, Hiroki; Uchida, Tomohiko; Muto, Mayumi; Uzawa, Akiyuki; Ito, Shoichi; Kuwabara, Satoshi

    2015-08-15

    Trigeminal root entry zone abnormality on brain magnetic resonance imaging has been frequently reported in multiple sclerosis patients, but it has not been investigated in neuromyelitis optica patients. Brain magnetic resonance imaging of 128 consecutive multiple sclerosis patients and 46 neuromyelitis optica patients was evaluated. Trigeminal root entry zone abnormality was present in 11 (8.6%) of the multiple sclerosis patients and two (4.3%) of the neuromyelitis optica patients. The pontine trigeminal root entry zone may be involved in both multiple sclerosis and neuromyelitis optica.

  11. Managing psychological stress in the multiple sclerosis medical visit: Patient perspectives and unmet needs.

    PubMed

    Senders, Angela; Sando, Kelsi; Wahbeh, Helané; Peterson Hiller, Amie; Shinto, Lynne

    2016-08-01

    Psychological stress can negatively impact multiple sclerosis. To further understand how stress is addressed in the multiple sclerosis medical visit, 34 people with multiple sclerosis participated in focus groups. Transcripts were analyzed by inductive thematic analysis. The majority of participants did not discuss stress with their provider, citing barriers to communication such as lack of time, poor coordination between specialties, physician reliance on pharmaceutical prescription, and patient lack of self-advocacy. Participants recommended several ways to better manage psychological well-being in the clinical setting. These findings provide a foundation for future studies aimed at minimizing the detrimental effect of stress in multiple sclerosis.

  12. Cerebrospinal Fluid Biomarkers for Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex.

    PubMed

    Nakayama, Yui; Morimoto, Satoru; Yoneda, Misao; Kuzuhara, Shigeki; Kokubo, Yasumasa

    2013-01-01

    Objective. Amyotrophic lateral sclerosis/parkinsonism-dementia complex is classified as one of the tauopathies. Methods. The total tau, phosphorylated tau, and amyloid β42 levels were assayed in cerebrospinal fluid from patients with Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (n = 12), Alzheimer's disease (n = 9), Parkinson's disease (n = 9), amyotrophic lateral sclerosis (n = 11), and controls (n = 5) using specific enzyme-linked immunosorbent assay methods. Results. Total tau and phosphorylated tau did not increase and amyloid β42 was relatively reduced in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex. Relatively reduced amyloid β42 might discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from amyotrophic lateral sclerosis and Parkinson's disease, and the ratios of phosphorylated-tau to amyloid β42 could discriminate Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer's disease. Conclusions. Cerebrospinal fluid analysis may be useful to differentiate amyotrophic lateral sclerosis/parkinsonism-dementia complex from Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease.

  13. New ACR EULAR guidelines for systemic sclerosis classification.

    PubMed

    Johnson, Sindhu R

    2015-05-01

    The American College of Rheumatology and European League Against Rheumatism classification criteria for systemic sclerosis are a significant advancement in the field. This article describes the innovative, rigorous, criteria development strategy that was used. The new criteria build upon previous criteria by incorporating important elements (proximal scleroderma, sclerodactyly, digital pits, pulmonary fibrosis, Raynaud's phenomenon, and scleroderma specific autoantibodies). The new criteria add emphasis to the vasculopathic manifestations, and include the early manifestation of puffy fingers. Together, these enhancements have resulted in a shift in the conceptual framework of the disease for the next generation. The new criteria have improved sensitivity and specifically, particularly among cases with early disease, mild disease, or limited disease. The ability to classify more cases, at an earlier stage, may confer the opportunity to intervene and prevent disease progression. Undoubtedly, this will lead to a paradigm shift in the conduct of clinical trials in systemic sclerosis.

  14. Pictorial review of intrathoracic manifestations of progressive systemic sclerosis

    PubMed Central

    AL-Jahdali, Hamdan; Rajiah, Prabhakar; Allen, Carolyn; Koteyar, Shyam Sunder; Khan, Ali Nawaz

    2014-01-01

    Intra-thoracic manifestations of progressive systemic sclerosis (PSS) are not well known particularly the imaging features, which forms the basis of accurate and timely diagnosis. The aim of this study is to familiarize the physicians and radiologists with these features. The diagnosis can remain elusive because of the non-specific nature of symptoms which mimic many common conditions. Thus, the diagnosis of PSS can be missed leading to continuous morbidity if the correct imaging is not pursued. The authors examined the records of rheumatology patient referrals of over a 5 year period. A hundred and seventy patients with systemic sclerosis and mixed connective tissue disorders were chosen for detailed study of the imaging available, which form the basis of this review. The images included conventional chest radiographs, digital radiographs computed radiography (CT) and high resolution computed tomography (HRCT). Where applicable computed pulmonary angiography (CTPA) and radionuclide scans were also interrogated. PMID:25276237

  15. [The brain structures functional activity and aggression patients' multiple sclerosis].

    PubMed

    Reznikova, T N; Seliverstova, N A; Kataeva, G V; Aroev, R A; Il'ves, A G; Kuznetsova, A K

    2015-01-01

    The article is devoted to investigation of unconscious aggression in patients with multiple sclerosis. We carried out comparison of the relative assessments of metabolism speed of glucose (according to positron emission tomography) and indicators of unconscious aggression (in the Hand test). It is shown that an increased tendency to open aggression (unconscious aggression) in patients with multiple sclerosis, is mainly linked with a reduction in the functioning of different departments of the frontal lobes of the brain on the left and with changes of the metabolism speed of glucose in the structures of the limbic system of the left and right hemisphere. With increasing of unconscious aggression we observed decrease of glucose metabolism speed in certain areas of the lower and middle frontal gyrus.

  16. Automated measurements of cerebral atrophy in multiple sclerosis.

    PubMed

    Hageleit, U; Will, C H; Seidel, D

    1987-01-01

    An automated method of measuring cerebral atrophy is introduced. Using this method we studied patients with multiple sclerosis and a control group showing premature cerebral atrophy in multiple sclerosis (P = 1,32 x 10(-8) for male and P = 3,6 x 10(-14) for female). There was only a weak correlation between cerebral atrophy and psychological deficits. Multivariate analysis did not show any significant correlation between cerebral atrophy, duration of disease, clinical manifestations and progression of disease. We conclude that our method to measure cerebral atrophy is more accurate and less time-consuming than the use of linear indices. It might be appropriate for further investigations in evaluating atrophic processes in cerebro-vascular, degenerative and exogen-toxic disease of brain.

  17. Multiple Sclerosis and Catastrophic Health Expenditure in Iran

    PubMed Central

    Juyani, Yaser; Hamedi, Dorsa; Hosseini Jebeli, Seyede Sedighe; Qasham, Maryam

    2016-01-01

    Background: There are many disabling medical conditions which can result in catastrophic health expenditure. Multiple Sclerosis is one of the most costly medical conditions through the world which encounter families to the catastrophic health expenditures. This study aims to investigate on what extent Multiple sclerosis patients face catastrophic costs. Method: This study was carried out in Ahvaz, Iran (2014). The study population included households that at least one of their members suffers from MS. To analyze data, Logit regression model was employed by using the default software STATA12. Results: 3.37% of families were encountered with catastrophic costs. Important variables including brand of drug, housing, income and health insurance were significantly correlated with catastrophic expenditure. Conclusions: This study suggests that although a small proportion of MS patients met the catastrophic health expenditure, mechanisms that pool risk and cost (e.g. health insurance) are required to protect them and improve financial and access equity in health care.

  18. [A review of multiple sclerosis (2). Diagnosis and treatment].

    PubMed

    Martinez-Altarriba, M C; Ramos-Campoy, O; Luna-Calcaño, I M; Arrieta-Antón, E

    2015-09-01

    Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although there are several hypotheses, such as infections or genetics. In its pathophysiology, it seems that immune activation attacks the myelin sheath, causing a progressive and irreversible axonal degeneration. The disease produces a variety of symptoms, and diagnosis requires fulfilling a number of criteria and the exclusion of other possible causes. The role of neuroimaging is very important, especially Magnetic Resonance Imaging. Despite the availability of disease-modifying drugs, none of them are able to halt its progress, and the most useful drugs are those designed to alleviate the symptoms of outbreaks. Overall, multiple sclerosis requires a significant effort in research to clarify not only why and how it occurs, as well as the development of new measures to improve quality of life of affected patients. PMID:25442466

  19. [A review of multiple sclerosis (1). Presentation of a case].

    PubMed

    Martinez-Altarriba, M C; Ramos-Campoy, O; Luna-Calcaño, I M; Arrieta-Antón, E

    2015-01-01

    Multiple sclerosis is a major demyelinating disease of the central nervous system. It has a significant economic and social impact. Its etiology is unclear, although there are several hypotheses, such as infections or genetics. In its pathophysiology, it seems that immune activation attacks the myelin sheath, causing a progressive and irreversible axonal degeneration. The disease produces a variety of symptoms, and diagnosis requires fulfilling a number of criteria and the exclusion of other possible causes. The role of neuroimaging, especially MRI, is very important. Despite the availability of disease-modifying drugs, none of them are able to halt its progress, and the most useful drugs are those designed to alleviate the symptoms of outbreaks. Overall, multiple sclerosis requires a significant effort in research to clarify not only why and how it occurs, but also to develop of new measures to improve the life of affected patients. PMID:25241121

  20. Theranostic Implications of Nanotechnology in Multiple Sclerosis: A Future Perspective

    PubMed Central

    Singh, Ajay Vikram; Khare, Manish; Gade, W. N.; Zamboni, Paolo

    2012-01-01

    Multiple Sclerosis is a multifactorial disease with several pathogenic mechanisms and pathways. Successful MS management and medical care requires early accurate diagnosis along with specific treatment protocols based upon multifunctional nanotechnology approach. This paper highlights advances in nanotechnology that have enabled the clinician to target the brain and CNS in patient with multiple sclerosis with nanoparticles having therapeutic and imaging components. The multipartite theranostic (thera(py) + (diag)nostics) approach puts forth strong implications for medical care and cure in MS. The current nanotheranostics utilize tamed drug vehicles and contain cargo, targeting ligands, and imaging labels for delivery to specific tissues, cells, or subcellular components. A brief overview of nonsurgical nanorepair advances as future perspective is also described. Considering the potential inflammatory triggers in MS pathogenesis, a multifunctional nanotechnology approach will be needed for the prognosis. PMID:23346386

  1. Major histocompatibility complex class II genes and systemic sclerosis.

    PubMed

    Briggs, D; Welsh, K I

    1991-11-01

    1. In no ethnic group is the overall association between systemic sclerosis and the MHC strong enough for direct clinical use. MHC associations do support the classification of the disease into limited cutaneous systemic sclerosis and diffuse cutaneous systemic sclerosis. 2. Indications are that associations between specific subsets of patients with systemic sclerosis and genetic markers will assume greater importance both diagnostically and prognostically. The group with lung fibrosis look prime candidates, for example. 3. Genetic markers are useful means of relating chemically induced systemic sclerosis like disorders with the classical disease. Vinyl chloride disease provides an example. 4. Evidence is emerging of strong associations between certain genetic markers and autoantibody production; a similar story has emerged in systemic lupus erythematosus. We believe that, eventually, genetic tests will be used to influence treatment in at least a subset of patients with systemic sclerosis but that a dramatic breakthrough will not be made until we know how the genetics of the disease relate to the primary biochemical disease characteristic--that is, the overproduction of collagen. In this respect it has been suggested that the 5' flanking DNA of dermal collagen genes is particularly susceptible to the action of Scl-70 (topoisomerase I). A problem is how to tie this and the other observations discussed above together. The association of autoantibodies with topoisomerase I provides a tentative link between the MHC and collagen gene expression. Although the role and reason for anti-Scl-70 in systemic sclerosis is unknown, humoral autoimmunity, at least in systemic lupus erythematosus, seems to be strongly dependent on specific HLA genes. With an understanding of the function of MHC products at the molecular level, HLA and disease associations can now be analysed on a mechanistic level. For insulin dependent diabetes mellitus it has been shown that the MHC determined

  2. Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis

    SciTech Connect

    Maddern, G.J.; Horowitz, M.; Jamieson, G.G.; Chatterton, B.E.; Collins, P.J.; Roberts-Thomson, P.

    1984-10-01

    Gastric and esophageal emptying were assessed using scintigraphic techniques in 12 patients with progressive systemic sclerosis and 22 normal volunteers. Esophageal emptying was significantly delayed in the patient group, with 7 of the 12 patients beyond the normal range. Gastric emptying was slower in patients than in controls, with 9 patients being outside the normal range for solid emptying and 7 patients outside the normal range for liquid emptying. Findings from gastric and esophageal emptying tests generally correlated well with symptoms of dysphagia and gastroesophageal reflux. However, 2 patients with normal emptying studies had symptomatic heartburn, and 2 patients with delay of both solid and liquid gastric emptying gave no history of gastroesophageal reflux. Delayed gastric emptying may be an important factor in the development of upper gastrointestinal symptoms in patients with progressive systemic sclerosis.

  3. Coincidental association of mycosis fungoides and occupational systemic sclerosis?

    PubMed

    Yasuda, Masahito; Amano, Hiroo; Yamanaka, Masayoshi; Tamura, Atsushi; Ishikawa, Osamu

    2008-01-01

    We report a 58-year-old man with mycosis fungoides (MF) and occupational systemic sclerosis (SSc) induced by silica exposure. He was engaged in tunnel construction from the age of 18 to 33 years. He developed MF at the age of 30. Diagnosis of silicosis was made at the age of 52 and SSc at the age of 58. Physical examinations revealed sclerotic skin changes on his forearms and fingers and poikiloderma on the left popliteal fossa and inguinal region. Both antinuclear antibody and antitopoisomerase-I antibody were positive. We could find no apparent difference between his clinical features and those of idiopathic SSc except for the presence of silicosis and MF. Systemic therapy with interferon-gamma for MF did not improve the skin sclerosis. We discuss the relationship of silica exposure to both MF and SSc.

  4. 7 Tesla MRI demonstrates vascular pathology in Balo's concentric sclerosis.

    PubMed

    Berghoff, M; Schlamann, M U; Maderwald, S; Grams, A E; Kaps, M; Ladd, M E; Gizewski, E R

    2013-01-01

    Baló's concentric sclerosis (BCS) is an inflammatory demyelinating disease related to multiple sclerosis; its underlying pathology remains unclear. At 7 T MRI in a 19-year-old female BCS patient, microhaemorrhages and ectatic veins were found in T2 hyperintense regions, features which have not been previously reported in conjunction with BCS, and these findings may support the view that vascular pathology plays a role in BCS. MRS data suggest that neuron loss and lipid turnover still took place months after a remission. Plasma exchange was effective in treating a relapse with severe motor deficits, and the off-label use of natalizumab was successful in maintaining remission in this patient.

  5. Transcranial magnetic stimulation in amyotrophic and primary lateral sclerosis.

    PubMed

    Cruz Martínez, A; Trejo, J M

    1999-01-01

    Conduction of the central motor pathways after transcranial magnetic stimulation (TMS) was investigated in 7 patients with amyotrophic lateral sclerosis (ALS) and 1 case with primary lateral sclerosis (PLS). Threshold intensity, central motor conduction time (CMCT) and amplitude of the motor evoked potentials (MEPs) were evaluated. Threshold was abnormal in 85% of tested limbs, and CMCT prolonged and amplitude of the MEPs attenuated in 28.5% of patients with ALS. Abnormal CMCT was asymmetric and related to clinical score. MEPs were absent in lower limbs in PLS, with prolonged or attenuated amplitude of the MEPs in upper limbs. EMG showed widespread signs of lower motor neuron involvement in ALS, but not in PLS. Cranial MRI showed frontoparietal cortical atrophy, more marked in pre-central gyrus, and SPECT there was lower tracer uptake in the perirolandic area in the PLS patient. EMG examination, TMS, cranial MRI and SPECT can help in the diagnosis of PLS.

  6. Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging.

    PubMed

    Ciccarelli, Olga; Barkhof, Frederik; Bodini, Benedetta; De Stefano, Nicola; Golay, Xavier; Nicolay, Klaas; Pelletier, Daniel; Pouwels, Petra J W; Smith, Seth A; Wheeler-Kingshott, Claudia A M; Stankoff, Bruno; Yousry, Tarek; Miller, David H

    2014-08-01

    The mechanisms underlying the pathogenesis of multiple sclerosis induce the changes that underpin relapse-associated and progressive disability. Disease mechanisms can be investigated in preclinical models and patients with multiple sclerosis by molecular and metabolic imaging techniques. Many insights have been gained from such imaging studies: persisting inflammation in the absence of a damaged blood-brain barrier, activated microglia within and beyond lesions, increased mitochondrial activity after acute lesions, raised sodium concentrations in the brain, increased glutamate in acute lesions and normal-appearing white matter, different degrees of demyelination in different patients and lesions, early neuronal damage in grey matter, and early astrocytic proliferation and activation in lesions and white matter. Clinical translation of molecular and metabolic imaging and extension of these techniques will enable the assessment of novel drugs targeted at these disease mechanisms, and have the potential to improve health outcomes through the stratification of patients for treatments.

  7. Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's syndrome.

    PubMed

    Parry-Jones, A R; Mitchell, J D; Gunarwardena, W J; Shaunak, S

    2008-04-01

    We describe a 32-year-old woman with sequential, severe, painless visual loss in one eye and then the other, and three temporally distinct episodes of neurological disturbance suggestive of demyelination in the spinal cord. She was positive for the T14484C mutation in the mitochondrial genome, one of three common mutations causing Leber's hereditary optic neuropathy. In addition, MRI identified areas of demyelination within the periventricular white matter of the brain and within the spinal cord. The coexistence of multiple sclerosis and Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more often than would be expected by chance; therefore, screening for the Leber's mutations in multiple sclerosis patients with severe visual loss should be considered because this has important prognostic and genetic implications.

  8. The Role of PPAR Gamma in Systemic Sclerosis.

    PubMed

    Dantas, Andréa Tavares; Pereira, Michelly Cristiny; de Melo Rego, Moacyr Jesus Barreto; da Rocha, Laurindo Ferreira; Pitta, Ivan da Rocha; Marques, Cláudia Diniz Lopes; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2015-01-01

    Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis. PMID:26064084

  9. Acquired convergence-evoked pendular nystagmus in multiple sclerosis.

    PubMed

    Barton, J J; Cox, T A; Digre, K B

    1999-03-01

    Nystagmus seen only with convergence is unusual. We describe four cases of acquired convergence-evoked pendular nystagmus in patients with multiple sclerosis. The nystagmus was horizontal and asymmetric in all patients. Eye movement recordings in one subject showed a conjugate rather than a convergent-divergent relationship of the phase of movement between the two eyes. All patients had evidence of optic neuropathy and cerebellar dysfunction. Occlusion of either eye during fixation of near targets led to divergent drift of the covered eye and a decrease in nystagmus. Intravenous scopolamine reduced nystagmus in one patient. Base-in prisms alleviated symptoms of oscillopsia at near and improving reading visual acuity. Convergence-evoked pendular nystagmus may be more common than currently appreciated, particularly among patients with multiple sclerosis.

  10. Pediatric multiple sclerosis: Perspectives from adolescents and their families.

    PubMed

    Krupp, Lauren B; Rintell, David; Charvet, Leigh E; Milazzo, Maria; Wassmer, Evangeline

    2016-08-30

    Supporting young people with pediatric multiple sclerosis can be challenging for families and health care providers. Adolescents may be more resilient than adults in reaction to the diagnosis but can have more difficulty planning for their futures. Appropriate, sensitive, and focused health provision should include consideration of the perspective of both the patient and parents. Multidisciplinary management strategies are often effective, as are referrals to programs that enhance individual and family coping and strengthen a sense of community. PMID:27572860

  11. Cluster headache-like pain in multiple sclerosis.

    PubMed

    Leandri, M; Cruccu, G; Gottlieb, A

    1999-10-01

    We describe a case with simultaneous occurrence of cluster headache-like pain and multiple sclerosis. Both neuroimaging and neurophysiology (trigeminal evoked potentials) revealed a demyelination plaque in the pons, at the trigeminal root entry zone, on the side of pain. Although that type of lesion is usually associated with trigeminal neuralgia pain, we hypothesize that in this case it may be linked with the concomitant cluster headache, possibly by activation of trigemino-vascular mechanisms.

  12. Is the frequency of multiple sclerosis increasing in Mexico?

    PubMed Central

    Gonzalez, O; Sotelo, J

    1995-01-01

    Multiple sclerosis has steadily increased in Mexican mestizos from an apparently rare disorder in the 1970s to the second most frequent cause of admission to a neurology ward in the 1990s. Most patients belonged to high socioeconomic and educational groups. Familial incidence was low. Age at onset was younger than in other series and long term disability was milder than in patients from countries in which the disease is apparently more prevalent. PMID:8530940

  13. Is the frequency of multiple sclerosis increasing in Mexico?

    PubMed

    Gonzalez, O; Sotelo, J

    1995-11-01

    Multiple sclerosis has steadily increased in Mexican mestizos from an apparently rare disorder in the 1970s to the second most frequent cause of admission to a neurology ward in the 1990s. Most patients belonged to high socioeconomic and educational groups. Familial incidence was low. Age at onset was younger than in other series and long term disability was milder than in patients from countries in which the disease is apparently more prevalent.

  14. Tuberous Sclerosis Complex: Diagnostic Role of Magnetic Resonance Imaging

    PubMed Central

    Sehgal, Virendra N; Singh, Navjeeven; Sharma, Sonal; Rohatgi, Jolly; Oberai, Rakesh; Chatterjee, Kingshuk

    2015-01-01

    Tuberous sclerosis complex (TSC) is a well-known clinical entity, characterized by facial angio-fibroma, shagreen patch, and hypo-melanotic, and confetti-like skin lesions. An exquisite fresh case is being narrated, emphasizing its microscopic pathology. The role of magnetic resonance imaging of the brain, in particular, is highlighted to define the large variety of neurological abrasions for determining its future progression. PMID:26288435

  15. Progressive systemic sclerosis occurring in patients exposed to chemicals.

    PubMed

    Czirják, L; Dankó, K; Schlammadinger, J; Surányi, P; Tamási, L; Szegedi, G Y

    1987-01-01

    Eight patients with systemic sclerosis previously exposed to organic chemical agents were investigated. Laboratory and clinical data of these patients were evaluated. The interval between the beginning of exposition and symptoms was 6.1 +/- 4.9 years. Considering the laboratory findings, a slight decrease in OKT4 positive T cell number was found. The antinucleolar and fine speckled antinuclear antibody pattern was found simultaneously in five cases. The possible role of chemical agents in the development of sclerodermic changes is discussed.

  16. Changing definitions of euphoria in multiple sclerosis: A short report.

    PubMed

    Duncan, Amy; Malcolm-Smith, Susan; Ameen, Ozayr; Solms, Mark

    2015-05-01

    A recent interest in euphoria in multiple sclerosis (MS) has resulted in a wealth of literature on this topic. However, a marked change in the definition of this symptom appears to have taken place since its first descriptions in the mid-19(th) century. This short report will demonstrate that the 'euphoria' being studied today may not be the same state as that originally observed and described in MS patients and some implications of this possibility are discussed. PMID:25204694

  17. Co-occurrence of multiple sclerosis and Parkinson disease

    PubMed Central

    Shaygannejad, Vahid; Shirmardi, Maryam; Dehghani, Leila; Maghzi, Helia

    2016-01-01

    Parkinson disease (PD) is a neurodegenerative disease of the central nervous system (CNS) with the highest prevalence in adults over 60 years of age On the other hand multiple sclerosis (MS), which mostly affects individuals between 20 and 40 years of age, is another neurodegenerative and autoimmune disease of the CNS, however, less common than PD. Here we aim to report the case of a 39-year-old woman, who developed PD 18 years after diagnosis of MS. PMID:27195248

  18. Co-occurrence of multiple sclerosis and Parkinson disease.

    PubMed

    Shaygannejad, Vahid; Shirmardi, Maryam; Dehghani, Leila; Maghzi, Helia

    2016-01-01

    Parkinson disease (PD) is a neurodegenerative disease of the central nervous system (CNS) with the highest prevalence in adults over 60 years of age On the other hand multiple sclerosis (MS), which mostly affects individuals between 20 and 40 years of age, is another neurodegenerative and autoimmune disease of the CNS, however, less common than PD. Here we aim to report the case of a 39-year-old woman, who developed PD 18 years after diagnosis of MS. PMID:27195248

  19. Clinical and molecular insights into tuberous sclerosis complex renal disease.

    PubMed

    Siroky, Brian J; Yin, Hong; Bissler, John J

    2011-06-01

    Patients with tuberous sclerosis complex are at great risk of developing renal lesions as part of their disease. These lesions include renal cysts and tumors. Significant advances in understanding the cell biology of these renal lesions has already led to clinical trials demonstrating that pharmacological interventions are likely possible. This review focuses on the pathology of these renal lesions, their underlying cell biology, and the possible therapeutic strategies that may prove to significantly improve care for these patients.

  20. Expression of DNA methylation genes in secondary progressive multiple sclerosis.

    PubMed

    Fagone, Paolo; Mangano, Katia; Di Marco, Roberto; Touil-Boukoffa, Chafia; Chikovan, Tinatin; Signorelli, Santo; Lombardo, Giuseppe A G; Patti, Francesco; Mammana, Santa; Nicoletti, Ferdinando

    2016-01-15

    Multiple sclerosis (MS) is an immunoinflammatory disease of the central nervous system that seems to be influenced by DNA methylation. We sought to explore the expression pattern of genes involved in the control of DNA methylation in Secondary Progressive (SP) MS patients' PBMCs. We have found that SP MS is characterized by a significant upregulation of two genes belonging to the MBD family genes, MBD2 and MBD4, and by a downregulation of TDG and TET3. PMID:26711572

  1. Pediatric multiple sclerosis: Perspectives from adolescents and their families.

    PubMed

    Krupp, Lauren B; Rintell, David; Charvet, Leigh E; Milazzo, Maria; Wassmer, Evangeline

    2016-08-30

    Supporting young people with pediatric multiple sclerosis can be challenging for families and health care providers. Adolescents may be more resilient than adults in reaction to the diagnosis but can have more difficulty planning for their futures. Appropriate, sensitive, and focused health provision should include consideration of the perspective of both the patient and parents. Multidisciplinary management strategies are often effective, as are referrals to programs that enhance individual and family coping and strengthen a sense of community.

  2. Teriflunomide for the treatment of relapsing-remitting multiple sclerosis.

    PubMed

    Miller, Aaron E

    2015-02-01

    Teriflunomide, a once-daily, oral disease-modifying therapy, is a valuable new treatment option for the management of patients with relapsing-remitting multiple sclerosis. This article reviews key efficacy and safety data arising from pivotal teriflunomide studies that demonstrate the utility in treating both treatment-naïve patients and those previously treated with another disease-modifying therapy who, for a variety of reasons, may require an alternative treatment. PMID:25511008

  3. Peripheral Vasculitis, Intermediate Uveitis and Interferon Use in Multiple Sclerosis

    PubMed Central

    Kinyas, Şeref; Esgin, Haluk

    2016-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. A 40-year-old female patient with a 12-year history of MS was admitted to our clinic with blurred vision and floaters in her right eye for about 1 month. Here, we share the findings and the management of intermediate uveitis and retinal periphlebitis in an MS case being treated with interferon beta-1a for 7 years. PMID:27800257

  4. Limited systemic sclerosis initially presenting with mesenteric panniculitis

    PubMed Central

    Arroyo-Ávila, Mariangelí; Vilá, Luis M

    2014-01-01

    Mesenteric panniculitis pertains to a group of uncommon disorders named sclerosing mesenteritis that present with different levels of inflammation and fibrosis of the small bowel mesentery. It is associated with abdominal surgeries, trauma, malignancies, infections and connective tissue diseases. To the best of our knowledge, no cases of sclerosing mesenteritis have been reported in patients with systemic sclerosis. We present a case of a 61-year-old woman who had incidental CT findings of mesenteric panniculitis. Diagnosis was confirmed by biopsy that showed fat necrosis. On further review she had a 1-year history of Raynaud's phenomenon. Physical examination showed sclerodactyly. She had elevated anticentromere antibodies and skin biopsy was consistent with scleroderma. She was diagnosed with limited systemic sclerosis and was treated with D-penicillamine. After 6 years of follow-up, the mesenteric panniculitis and systemic sclerosis both remained stable. This case highlights the importance of considering rheumatic diseases in the differential diagnosis of sclerosing mesenteritis. PMID:25326572

  5. Hepatoportal Sclerosis in Childhood: Descriptive Analysis of 12 Patients

    PubMed Central

    Gerenli, Nelgin; Ertekin, Vildan; Güllüoğlu, Mine; Durmaz, Özlem

    2013-01-01

    Hepatoportal sclerosis (HPS) is defined as sclerosis of portal areas in the absence of cirrhosis. There is little information about HPS in children in the literature. The aim of this study was to describe the clinical presentation, associated disorders, laboratory characteristics and outcome of children who were diagnosed as HPS. This study included 12 children diagnosed as HPS by the Pathology Department between 2005 and 2011. Data were collected from the gastroenterology clinic charts retrospectively, including demographics, presentation characteristics, laboratory data and recent status of patients. Twelve patients were enrolled (6 girls, 6 boys). The median age of patients was 13.5 yr. Median age at the time of biopsy was 11 yr. Four patients had splenomegaly, 3 had esophageal varices, one had hepatopulmonary syndrome and had been transplanted. Smooth muscle antibody was found positive in 4 patients, without autoimmune hepatitis findings in liver biopsy. One patient had celiac disease and another patient had positive celiac disease serology but pathology findings. Another patient had Turner's syndrome. Mean follow-up time was 39 months (3.3 yr) after biopsy. Hepatoportal sclerosis does not necessarily present with portal hypertension in children. PMID:24133357

  6. Spasticity in multiple sclerosis and role of glatiramer acetate treatment

    PubMed Central

    Meca-Lallana, Jose Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

    2015-01-01

    Introduction Spasticity is one of the most disabling and difficult-to-treat symptoms shown by patients with multiple sclerosis, who often show a suboptimal and unsatisfactory response to classic treatment and new available nonpharmacological alternatives. Due to the progressive nature of this condition, the early management should be essential to improve long-term outcomes. Methods We performed a narrative literature review of the contribution of spasticity to the burden of multiple sclerosis and the potential role of classic disease-modifying drugs. Results Added to the underlying pathophysiology of spasticity, certain external factors and drugs such as interferon may exacerbate the existing condition, hence their awareness is crucial as part of an effective management of spasticity. Furthermore, the evidence for the effectiveness of glatiramer acetate in preventing spasticity in naïve patients and in those switching from interferon should not be ignored. Conclusions This literature review proposes the examination of spasticity and the influence of classic disease-modifying agents on the level of existing condition among the variables to be considered when deciding on therapy for multiple sclerosis in clinical practice. PMID:26445705

  7. Ocular contrapulsion in multiple sclerosis: clinical features and pathophysiological mechanisms

    PubMed Central

    Frohman, E; Frohman, T; Fleckenstein, J; Racke, M; Hawker, K; Kramer, P

    2001-01-01

    The objective was to describe in multiple sclerosis, a cerebellar eye movement syndrome that resulted from an acute episode of inflammatory demyelination. Contrapulsion is an ocular motor disturbance characterised by a triad of (1) hypermetric saccadic eye movements in a direction opposite from a precisely localised lesion within a specific white matter pathway, the uncinate fasciculus, at the level of the superior cerebellar peduncle (SCP); (2) hypometric saccades towards the side of the lesion; (3) oblique saccades directed away from the side of the lesion on attempted vertical saccades.
 Infrared oculography was used to demonstrate the characteristic features of contrapulsion in two patients with multiple sclerosis.
 Brain MRI showed lesions within the region of the uncinate fasciculus and superior cerebellar peduncle in both patients. Eye movement recordings showed saccadic hypermetria away from the side of the lesion and saccadic hypometria towards the side of the lesion. The hypometria decomposed into a series of stepwise movements as the eye approached the target. Oblique saccades directed away from the side of the lesion were seen on attempted vertical saccades.
In conclusion, ocular contrapulsion can be seen in patients with multiple sclerosis and results from a lesion in the region of the SCP, involving the uncinate fasciculus.

 PMID:11309470

  8. Epidemiology of multiple sclerosis in U. S. veterans: 2. Latitude, climate and the risk of multiple sclerosis

    SciTech Connect

    Norman, J.E. Jr.; Kurtzke, J.F.; Beebe, G.W.

    1983-01-01

    An analysis of ten climatic factors and elevation for the counties of birth of 4371 U.S. white male veterans with multiple sclerosis and matched controls has been made in relation to birthplace latitude. The climatic factors include an air pollution index, concentrations of minerals in ground water, measures of annual solar radiation, both in energy per unit area and in hours of sunshine, mean annual periods of high and low temperatures, and measures of annual rainfall and average humidity. These variables all significantly influence the risk of multiple sclerosis when analyzed alone, but when they are adjusted for latitude, their effect is found to be due to their correlation with this variable.

  9. The risk to relatives of patients with sporadic amyotrophic lateral sclerosis.

    PubMed

    Hanby, Martha F; Scott, Kirsten M; Scotton, William; Wijesekera, Lokesh; Mole, Thomas; Ellis, Catherine E; Leigh, P Nigel; Shaw, Christopher E; Al-Chalabi, Ammar

    2011-12-01

    Amyotrophic lateral sclerosis is a neurodegenerative disease of motor neurons with a median survival of 2 years. Most patients have no family history of amyotrophic lateral sclerosis, but current understanding of such diseases suggests there should be an increased risk to relatives. Furthermore, it is a common question to be asked by patients and relatives in clinic. We therefore set out to determine the risk of amyotrophic lateral sclerosis to first degree relatives of patients with sporadic amyotrophic lateral sclerosis attending a specialist clinic. Case records of patients with sporadic amyotrophic lateral sclerosis seen at a tertiary referral centre over a 16-year period were reviewed, and pedigree structures extracted. All individuals who had originally presented with sporadic amyotrophic lateral sclerosis, but who subsequently had an affected first degree relative, were identified. Calculations were age-adjusted using clinic population demographics. Probands (n = 1502), full siblings (n = 1622) and full offspring (n = 1545) were identified. Eight of the siblings and 18 offspring had developed amyotrophic lateral sclerosis. The unadjusted risk of amyotrophic lateral sclerosis over the observation period was 0.5% for siblings and 1.0% for offspring. Age information was available for 476 siblings and 824 offspring. For this subset, the crude incidence of amyotrophic lateral sclerosis was 0.11% per year (0.05-0.21%) in siblings and 0.11% per year (0.06-0.19%) in offspring, and the clinic age-adjusted incidence rate was 0.12% per year (0.04-0.21%) in siblings. By age 85, siblings were found to have an 8-fold increased risk of amyotrophic lateral sclerosis, in comparison to the background population. In practice, this means the risk of remaining unaffected by age 85 dropped from 99.7% to 97.6%. Relatives of people with sporadic amyotrophic lateral sclerosis have a small but definite increased risk of being affected.

  10. Focal thinning of the cerebral cortex in multiple sclerosis.

    PubMed

    Sailer, Michael; Fischl, Bruce; Salat, David; Tempelmann, Claus; Schönfeld, Mircea Ariel; Busa, Evelina; Bodammer, Nils; Heinze, Hans-Jochen; Dale, Anders

    2003-08-01

    Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo, the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T2 hyper-intense and T1 hypo-intense lesion volumes. High-resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age-matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject's entire brain and computed cross-subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T2 and T1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm

  11. Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.

    PubMed

    Sahin, Mustafa; Henske, Elizabeth P; Manning, Brendan D; Ess, Kevin C; Bissler, John J; Klann, Eric; Kwiatkowski, David J; Roberds, Steven L; Silva, Alcino J; Hillaire-Clarke, Coryse St; Young, Lisa R; Zervas, Mark; Mamounas, Laura A

    2016-07-01

    On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame. PMID:27267556

  12. Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

    ERIC Educational Resources Information Center

    Learmonth, Yvonne C.; Paul, Lorna; McFadyen, Angus K.; Mattison, Paul; Miller, Linda

    2012-01-01

    The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures--the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale--in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended…

  13. Quality of life in multiple sclerosis in France, Germany, and the United Kingdom

    PubMed Central

    Murphy, N; Confavreux, C; Haas, J; Konig, N; Roullet, E; Sailer, M; Swash, M; Young, C; J-L, M.

    1998-01-01

    OBJECTIVE—To assess the quality of life (QoL) of patients with multiple sclerosis in France, Germany, and the United Kingdom with a cross sectional study.
METHODS—Patients were classified into three severity groups according to the expanded disability severity scale (EDSS); stage I, II, and III, corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS 6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis and 30 control patients without multiple sclerosis were recruited in each country. Control patients were matched to the patients with multiple sclerosis according to age and sex. Quality of life was assessed using the functional status questionnaire (FSQ).
RESULTS—The aspects of QoL that were mostly affected in the three countries under study were physical function and general wellbeing. Social role function decreased with increased severity of disease in France and in particular in Germany. Multiple sclerosis did not seem to have an impact on psychological function. The QoL of control patients was systematically higher than that of patients with multiple sclerosis.
CONCLUSIONS—Use of such a generic scale showed that progression of multiple sclerosis is accompanied by a decrease in QoL and suggested that this could be a relevant measurement in assessing the effect of treatment and progression of disease. Variation between countries, however, may be important.

 PMID:9771766

  14. Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference.

    PubMed

    Sahin, Mustafa; Henske, Elizabeth P; Manning, Brendan D; Ess, Kevin C; Bissler, John J; Klann, Eric; Kwiatkowski, David J; Roberds, Steven L; Silva, Alcino J; Hillaire-Clarke, Coryse St; Young, Lisa R; Zervas, Mark; Mamounas, Laura A

    2016-07-01

    On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame.

  15. 76 FR 78823 - Schedule for Rating Disabilities; Evaluation of Amyotrophic Lateral Sclerosis

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-20

    ... Sclerosis AGENCY: Department of Veterans Affairs. ACTION: Final rule. SUMMARY: The Department of Veterans... criterion provided for amyotrophic lateral sclerosis (ALS) to provide an evaluation of 100 percent for any... INFORMATION: On June 23, 2010, VA published in the Federal Register (75 FR 35711) a proposed rule that...

  16. Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis.

    PubMed

    Biswas, Sangita; Benedict, Stephen H; Lynch, Sharon G; LeVine, Steven M

    2012-06-07

    Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis.

  17. Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research.

    PubMed

    Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

    2014-09-01

    The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood-and adolescent-onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

  18. Complications in the treatment of oropharyngeal carcinoma in patients with systemic sclerosis: A case report.

    PubMed

    Coček, Ales; Hahn, Ales; Ambruš, Miloslav; Valešová, Marie

    2015-01-01

    Systemic sclerosis is a chronic, progressive disease with an extremely poor prognosis. The incidence of malignant tumors in patients with systemic sclerosis is increased when compared with that of the general population. In certain malignancies, systemic sclerosis presents as a paraneoplastic process. The symptoms of sclerosis in the organs of the head and neck often overlap with symptoms of malignant diseases, which may increase the difficulty of a differential diagnosis. Additionally, the presence of sclerosis may complicate standard examination procedures, due to poor access to the oral cavity and oropharynx. When considering treatment options, it is important to evaluate the surgical and oncological risks to soft tissues of the head and neck with regard to both diseases, as well as the relatively poor prognosis for systemic sclerosis and oropharyngeal cancer. The low incidence of patients with systemic sclerosis and oropharyngeal carcinoma together presents a clear case for a casuistic approach. Based upon our own experience, we can attest to the difficulty of treating such patients. However, we have no evidence to indicate that these patients have reduced tolerance to surgical treatments. The current study presents the case of a 47-year-old female with systemic sclerosis, who was diagnosed with oropharyngeal carcinoma. The patient initially tolerated radiotherapy treatment well, however post-radiotherapy complications occurred. Despite many enigmatic indications to the contrary, it appears that the complications in this instance may be due to late toxicity from radiotherapy.

  19. Complications in the treatment of oropharyngeal carcinoma in patients with systemic sclerosis: A case report

    PubMed Central

    ČOČEK, ALES; HAHN, ALES; AMBRUŠ, MILOSLAV; VALEŠOVÁ, MARIE

    2015-01-01

    Systemic sclerosis is a chronic, progressive disease with an extremely poor prognosis. The incidence of malignant tumors in patients with systemic sclerosis is increased when compared with that of the general population. In certain malignancies, systemic sclerosis presents as a paraneoplastic process. The symptoms of sclerosis in the organs of the head and neck often overlap with symptoms of malignant diseases, which may increase the difficulty of a differential diagnosis. Additionally, the presence of sclerosis may complicate standard examination procedures, due to poor access to the oral cavity and oropharynx. When considering treatment options, it is important to evaluate the surgical and oncological risks to soft tissues of the head and neck with regard to both diseases, as well as the relatively poor prognosis for systemic sclerosis and oropharyngeal cancer. The low incidence of patients with systemic sclerosis and oropharyngeal carcinoma together presents a clear case for a casuistic approach. Based upon our own experience, we can attest to the difficulty of treating such patients. However, we have no evidence to indicate that these patients have reduced tolerance to surgical treatments. The current study presents the case of a 47-year-old female with systemic sclerosis, who was diagnosed with oropharyngeal carcinoma. The patient initially tolerated radiotherapy treatment well, however post-radiotherapy complications occurred. Despite many enigmatic indications to the contrary, it appears that the complications in this instance may be due to late toxicity from radiotherapy. PMID:25435929

  20. Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis

    PubMed Central

    2012-01-01

    Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis. PMID:22676575

  1. Is Hypovitaminosis D One of the Environmental Risk Factors for Multiple Sclerosis?

    ERIC Educational Resources Information Center

    Pierrot-Deseilligny, Charles; Souberbielle, Jean-Claude

    2010-01-01

    The role of hypovitaminosis D as a possible risk factor for multiple sclerosis is reviewed. First, it is emphasized that hypovitaminosis D could be only one of the risk factors for multiple sclerosis and that numerous other environmental and genetic risk factors appear to interact and combine to trigger the disease. Secondly, the classical…

  2. Lou Gehrig and amyotrophic lateral sclerosis. Is vitamin E to be revisited?

    PubMed

    Reider, C R; Paulson, G W

    1997-05-01

    Investigators are beginning to reexamine the use of vitamin E for the treatment of amyotrophic lateral sclerosis. Vitamin E was isolated in the 1920s, and the results of animal studies led rapidly to clinical use. Regrettably, vitamin E did not ameliorate the progression of amyotrophic lateral sclerosis for Lou Gehrig, but more recent advances may identify subpopulations that do respond to vitamin E.

  3. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

    PubMed Central

    Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

    2015-01-01

    Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

  4. Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application.

    PubMed

    Bambo, Maria Pilar; Garcia-Martin, Elena; Perez-Olivan, Susana; Larrosa-Povés, José Manuel; Polo-Llorens, Vicente; Gonzalez-De la Rosa, Manuel

    2016-01-01

    Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in patients with multiple sclerosis. Here, we describe the emergence of an idea to quantify these optic disc color changes in multiple sclerosis patients. We recruited 12 multiple sclerosis patients with previous optic neuritis attack and obtained photographs of their optic discs. The Laguna ONhE, a new colorimetric software using hemoglobin as the reference pigment in the papilla, was used for the analysis. The papilla of these multiple sclerosis patients showed greater pallor, especially in the temporal sector. The software detected the pallor and assigned hemoglobin percentages below normal reference values. Measurements of optic disc hemoglobin levels obtained with the Laguna ONhE software program had good ability to detect optic atrophy and, consequently, axonal loss in multiple sclerosis patients. This new technology is easy to implement in routine clinical practice.

  5. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis.

    PubMed

    Weisfeld-Adams, James D; Katz Sand, Ilana B; Honce, Justin M; Lublin, Fred D

    2015-03-01

    Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient's 'multiple sclerosis-like' phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis.

  6. Multiple sclerosis presenting as neurological decompression sickness in a U.S. navy diver.

    PubMed

    Jan, Moore H; Jankosky, Christopher J

    2003-02-01

    A case of clinically definite multiple sclerosis presenting as neurological decompression sickness is presented. A 23-yr-old U.S. Navy diver experienced onset of hypesthesia of the left upper trunk approximately 19 h after making two SCUBA dives. She did not seek medical attention until 3 wk later, at which time she was diagnosed with possible neurological decompression sickness. She was treated with hyperbaric oxygen, but demonstrated no improvement. Further evaluation led to the diagnosis of multiple sclerosis. This case underscores the potential similarity in neurological presentation between multiple sclerosis and decompression sickness. The differential diagnosis of neurological decompression sickness, particularly in atypical cases, should include multiple sclerosis. The appropriateness of medically clearing multiple sclerosis patients for diving is discussed.

  7. Association between alcohol consumption and amyotrophic lateral sclerosis: a meta-analysis of five observational studies.

    PubMed

    E, Meng; Yu, Sufang; Dou, Jianrui; Jin, Wu; Cai, Xiang; Mao, Yiyang; Zhu, Daojian; Yang, Rumei

    2016-08-01

    The purpose of this study is to examine the association between alcohol consumption and amyotrophic lateral sclerosis. Published literature on the association between alcohol consumption and amyotrophic lateral sclerosis was retrieved from the PubMed and Embase databases. Two authors independently extracted the data. The quality of the identified studies was evaluated according to the Newcastle-Ottawa scale. Subgroup and sensitivity analyses were performed and publication bias was assessed. Five articles, including one cohort study and seven case-control studies, and a total of 431,943 participants, were identified. The odds ratio for the association between alcohol consumption and amyotrophic lateral sclerosis was 0.57 (95 % confidence interval 0.51-0.64). Subgroup and sensitivity analyses confirmed the result. Evidence for publication bias was detected. Alcohol consumption reduced the risk of developing amyotrophic lateral sclerosis compared with non-drinking. Alcohol, therefore, has a potentially neuroprotective effect on the development of amyotrophic lateral sclerosis.

  8. Epstein–Barr virus infection is not a characteristic feature of multiple sclerosis brain

    PubMed Central

    Willis, Simon N.; Stadelmann, Christine; Rodig, Scott J.; Caron, Tyler; Gattenloehner, Stefan; Mallozzi, Scott S.; Roughan, Jill E.; Almendinger, Stefany E.; Blewett, Megan M.; Brück, Wolfgang; Hafler, David A.

    2009-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS) that is thought to be caused by a combination of genetic and environmental factors. To date, considerable evidence has associated Epstein–Barr virus (EBV) infection with disease development. However, it remains controversial whether EBV infects multiple sclerosis brain and contributes directly to CNS immunopathology. To assess whether EBV infection is a characteristic feature of multiple sclerosis brain, a large cohort of multiple sclerosis specimens containing white matter lesions (nine adult and three paediatric cases) with a heterogeneous B cell infiltrate and a second cohort of multiple sclerosis specimens (12 cases) that included B cell infiltration within the meninges and parenchymal B cell aggregates, were examined for EBV infection using multiple methodologies including in situ hybridization, immunohistochemistry and two independent real-time polymerase chain reaction (PCR) methodologies that detect genomic EBV or the abundant EBV encoded RNA (EBER) 1, respectively. We report that EBV could not be detected in any of the multiple sclerosis specimens containing white matter lesions by any of the methods employed, yet EBV was readily detectable in multiple Epstein–Barr virus-positive control tissues including several CNS lymphomas. Furthermore, EBV was not detected in our second cohort of multiple sclerosis specimens by in situ hybridization. However, our real-time PCR methodologies, which were capable of detecting very few EBV infected cells, detected EBV at low levels in only 2 of the 12 multiple sclerosis meningeal specimens examined. Our finding that CNS EBV infection was rare in multiple sclerosis brain indicates that EBV infection is unlikely to contribute directly to multiple sclerosis brain pathology in the vast majority of cases. PMID:19638446

  9. The role of information system in multiple sclerosis management

    PubMed Central

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-01-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management. PMID:25709660

  10. Patient perceptions of multiple sclerosis and its treatment

    PubMed Central

    de Seze, Jérôme; Borgel, Florent; Brudon, Frédérique

    2012-01-01

    Background In order to improve the treatment outcome in multiple sclerosis, it is important to document the factors that influence adherence to therapy. The purpose of this study was to determine patient perceptions and awareness of multiple sclerosis and its treatment, treatment adherence, and impact on quality of life and daily living. Methods This was a cross-sectional observational study performed in France. Each participating neurologist included the first three patients with relapsing-remitting multiple sclerosis who consulted after the start of the study. Data on clinical features were collected from a physician questionnaire and on disease and treatment perception and on quality of life from a patient autoquestionnaire. Results A total of 175 neurologists entered 202 patients in the study. The mean duration of disease was 8.0 ± 7.0 years, and immunomodulatory treatment had been administered for a mean duration of 3.0 ± 2.0 years. A total of 166 patients (82.2%) were treated with interferon-β preparations and 36 patients (17.8%) with glatiramer acetate. Eighty-five patients (42.1%) reported missing their injections from time to time and 36 patients (17.8%) reported “drug holidays”. The most frequently given reason for nonadherence was forgetfulness (38.7% of cases). Eighty-six patients (42.6%) and 70 patients (34.7%) claimed to be well informed about their disease and treatment, respectively. Adherence was significantly higher in well informed patients (P = 0.035). The majority of patients (176 patients, 87.1%) intended continuing their current treatment and 49.5% considered that their current treatment might reduce relapses. The most frequently reported side effect was muscle pain (124 patients, 61.4%). Conclusion Patient understanding of treatment for disease enhances treatment adherence. Greater patient involvement in disease management requires better communication between physicians and their patients. PMID:22536062

  11. The role of information system in multiple sclerosis management.

    PubMed

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-12-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management.

  12. Coordinate expression of AOS genes and JA accumulation: JA is not required for initiation of closing layer in wound healing tubers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wounding induces a series of coordinated physiological responses essential for protection and healing of the damaged tissue. Wound-induced formation of jasmonic acid (JA) is important in defense responses in leaves, but comparatively little is known about the induction of JA biosynthesis and its ro...

  13. Estimating Typical Multiple Sclerosis Disability Progression Speed from Clinical Observations

    PubMed Central

    Brown, Murray G.; Asbridge, Mark; Hicks, Vern; Kirby, Sarah; Murray, Thomas J.; Andreou, Pantelis; Lin, Dong

    2014-01-01

    Introduction Multiple sclerosis (MS) is a chronic disease of the central nervous system. Estimates of MS natural history (NH) disability progression speed from clinical observations vary worldwide. This may reflect, in part, variance in censoring-bias) (missing observations) and assumptions about when irreversible disability progression events occurred. We test whether estimates of progression speed which assume midpoint survival time at irreversible disability endpoints are significantly faster than estimates which assume maximum survival time, and are more stable across study groups and time periods. Methods Our Nova Scotia NH study population includes 2,240 definite relapsing-onset multiple sclerosis (R-MS) natural history patients with 18,078 Expanded Disability Status Scale (EDSS) clinical observations in study period 1979–2010. Progression speed is measured by rate-of-change in range EDSS 0–6 and by survival time at irreversible endpoints EDSS 1–9. Midpoint censoring-bias-reduction methods are applied to clinical observations. Findings Typical EDSS increase per year in range EDSS 0–6, assuming midpoint survival time, is estimated to be 0.168 for all R-MS, 0.204 for eventually-DMD-treated patients and 0.155 for never-DMD-treated patients. Estimates assuming midpoint rather than maximum survival time are significantly faster: 16% faster for all R-MS natural history patients, 6% faster for eventually-DMD-treated patients, and 21% faster for never-DMD-treated patients. The variability of estimates across study groups and time periods decreased when midpoint survival time was assumed. Conclusions Estimates of typical disease progression speed from 1979–2010 Nova Scotia clinical observations are sensitive to censoring-bias and to analysts’ survival time assumptions. Censoring-bias-adjusted estimates of typical natural history disability progression speed in relapsing-onset multiple sclerosis patients are significantly faster, and less variable within

  14. Nature plus nurture: the triggering of multiple sclerosis.

    PubMed

    Wekerle, Hartmut

    2015-01-01

    Recent clinical and experimental studies indicate that multiple sclerosis develops as consequence of a failed interplay between genetic ("nature") and environmental ("nurture") factors. A large number of risk genes favour an autoimmune response against the body's own brain matter. New experimental data indicate that the actual trigger of this attack is however provided by an interaction of brain-specific immune cells with components of the regular commensal gut flora, the intestinal microbiota. This concept opens the way for new therapeutic approaches involving modulation of the microbiota by dietary or antibiotic regimens. PMID:26430854

  15. [Hemorrhagic tuberous sclerosis. Report of a Jehovah Witness patient].

    PubMed

    Azócar, G; Castillo, O; Van Cauwelaert, R; Aguirre, C; Wöhler, C; Wash, A

    1999-11-01

    We report a 26 years old male with a tuberous sclerosis with multiple and bilateral kidney cysts and angiomyolipomas. The patient presented to the emergency room with a severe abdominal pain and anemia, secondary to a bleeding angiomyolipoma. The patient rejected blood transfusions due to his religious beliefs. A selective angiography was performed confirming diagnosis and the lesion artery was selectively embolized, stopping the bleeding immediately. The patient had a satisfactory evolution thereafter. This is a rare lesion and the fact that the patient was a Jehovah witness that rejected blood transfusions, required an innovative medical approach. PMID:10835724

  16. [Dysfunction of mitochondrial dynamic and distribution in Amyotrophic Lateral Sclerosis].

    PubMed

    Walczak, Jarosław; Szczepanowska, Joanna

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a complex disease leading to degradation of motor neurons. One of the early symptoms of many neurodegenerative disorders are mitochondrial dysfunctions. Since few decades mitochondrial morphology changes have been observed in tissues of patients with ALS. Mitochondria are highly dynamic organelles which constantly undergo continuous process of fusion and fission and are actively transported within the cell. Proper functioning of mitochondrial dynamics and distribution is crucial for cell survival, especially neuronal cells that have long axons. This article summarizes the current knowledge about the role of mitochondrial dynamics and distribution in pathophysiology of familial and sporadic form of ALS. PMID:26689011

  17. Microvesicles: What is the Role in Multiple Sclerosis?

    PubMed Central

    Carandini, Tiziana; Colombo, Federico; Finardi, Annamaria; Casella, Giacomo; Garzetti, Livia; Verderio, Claudia; Furlan, Roberto

    2015-01-01

    Microvesicles are a recently described way of cell communication that has been implicated in a number of biological processes, including neuroinflammation. Widely investigated as biomarkers in oncology and neurological disorders, little is known of the role of microvesicles in the pathogenesis of diseases such as multiple sclerosis (MS). Several evidences suggest that pro-inflammatory microglia and infiltrating macrophages release microvesicles that spread inflammatory signals and alter neuronal functions. We review here available information on microvesicles, with a special focus on microglia and macrophage microvesicles, in the pathogenesis of MS, and as potential biomarkers and therapeutic targets. PMID:26074867

  18. The clinical relevance of sexual dysfunction in systemic sclerosis.

    PubMed

    Bruni, C; Raja, J; Denton, C P; Matucci-Cerinic, M

    2015-12-01

    Systemic sclerosis is a chronic multi-organ autoimmune disease, leading to important clinical and psychological implications. Among organ complications, sexual dysfunction is a major issue for both male and female gender, with high prevalence and great impact on quality of life, although frequently not addressed by both clinicians and patients. While erectile dysfunction is the most common cause of sexual problems in males, genital tract and general physical changes are major contributors to sexual impairment in females. This review presents current state of the art on this topic, discussing published data on presentation, evaluation and therapeutic options.

  19. Cardiogenic shock in a young female with multiple sclerosis.

    PubMed

    Uriel, Nir; Kaluski, Edo; Hendler, Alberto; Leitman, Marina; Vered, Zvi

    2006-07-01

    A 24-year-old patient with no previous cardiovascular illness or symptoms, was admitted in profound cardiogenic shock related to severe left ventricular systolic dysfunction, accompanied by multiple sclerosis (MS) exacerbation. Initially the patient required mechanical ventilation, inotropic support, and intra-aortic balloon counter-pulsation along with invasive haemodynamic monitoring. Within a few days of high dose corticosteroid therapy patients left ventricular systolic dysfunction returned almost completely to normal, and this was accompanied by dramatic clinical improvement. We review the current literature on the relation between MS and left ventricular systolic dysfunction and heart failure.

  20. Immunopathology of Japanese macaque encephalomyelitis is similar to multiple sclerosis.

    PubMed

    Blair, Tiffany C; Manoharan, Minsha; Rawlings-Rhea, Stephanie D; Tagge, Ian; Kohama, Steven G; Hollister-Smith, Julie; Ferguson, Betsy; Woltjer, Randall L; Frederick, Meredith C; Pollaro, James; Rooney, William D; Sherman, Larry S; Bourdette, Dennis N; Wong, Scott W

    2016-02-15

    Japanese macaque encephalomyelitis (JME) is an inflammatory demyelinating disease that occurs spontaneously in a colony of Japanese macaques (JM) at the Oregon National Primate Research Center. Animals with JME display clinical signs resembling multiple sclerosis (MS), and magnetic resonance imaging reveals multiple T2-weighted hyperintensities and gadolinium-enhancing lesions in the central nervous system (CNS). Here we undertook studies to determine if JME possesses features of an immune-mediated disease in the CNS. Comparable to MS, the CNS of animals with JME contain active lesions positive for IL-17, CD4+ T cells with Th1 and Th17 phenotypes, CD8+ T cells, and positive CSF findings.

  1. Saffold cardiovirus and multiple sclerosis: no evidence for an association

    PubMed Central

    Galama, Jochem M D; Zoll, Jan G; Lanke, Kjerstin H; de Jong, Arjan S; Melief, Jeroen; Huitinga, Inge; Verbeek, Marcel M; van Kuppeveld, Frank J M

    2014-01-01

    Saffold cardiovirus, a newly discovered human cardiovirus, has close similarity with Theiler's murine encephalomyelitis virus (TMEV) which can cause a chronic demyelinating encephalomyelitis in mice. In this study, we tested whether Saffold cardiovirus infection of the brain is associated with multiple sclerosis (MS). Autopsy white matter samples from 19 MS and 9 normal brain donors were tested by polymerase chain reaction. All were negative. Paired cerebrospinal fluid and serum samples from 24 MS patients and 27 controls were tested for Saffold cardiovirus-specific oligoclonal bands, two patients and two controls reacted positive. We conclude that an association between Saffold cardiovirus and MS is highly improbable. PMID:25356431

  2. Evidence-based Management of Rapidly Progressing Systemic Sclerosis

    PubMed Central

    Khanna, Dinesh; Denton, Christopher P.

    2009-01-01

    Systemic sclerosis has the highest case-specific mortality of any of the autoimmune rheumatic diseases as well as causing major morbidity. It is a major clinical challenge and one that has previously provoked substantial nihilism due to the limited therapeutic options available and perceived lack of evidence for clinical effectiveness of those treatments that are currently in use. However this situation is changing and there are emerging data supporting efficacy for some treatment approaches for this patient group together with a growing number of exciting potential novel approaches to treatment that are moving into the clinical arena. Some of the recent clinical trials are reviewed and discussed in detail. PMID:20534372

  3. Abnormal Control of Orbicularis Oculi Reflex Excitability in Multiple Sclerosis

    PubMed Central

    Cabib, Christopher; Llufriu, Sara; Martinez-Heras, Eloy; Saiz, Albert; Valls-Solé, Josep

    2014-01-01

    Brain lesions in patients with multiple sclerosis may lead to abnormal excitability of brainstem reflex circuits because of impairment of descending control pathways. We hypothesized that such abnormality should show in the analysis of blink reflex responses in the form of asymmetries in response size. The study was done in 20 patients with relapsing-remitting multiple sclerosis and 12 matched healthy subjects. We identified first patients with latency abnormalities (AbLat). Then, we analyzed response size by calculating the R2c/R2 ratio to stimulation of either side and the mean area of the R2 responses obtained in the same side. Patients with significantly larger response size with respect to healthy subjects in at least one side were considered to have abnormal response excitability (AbEx). We also examined the blink reflex excitability recovery (BRER) and prepulse inhibition (BRIP) of either side in search for additional indices of asymmetry in response excitability. Neurophysiological data were correlated with MRI-determined brain lesion-load and volume. Eight patients were identified as AbLat (median Expanded Disability Status Scale–EDSS = 2.75) and 7 of them had ponto-medullary lesions. Nine patients were identified as AbEx (EDSS = 1.5) and only 2 of them, who also were AbLat, had ponto-medullary lesions. In AbEx patients, the abnormalities in response size were confined to one side, with a similar tendency in most variables (significantly asymmetric R1 amplitude, BRER index and BRIP percentage). AbEx patients had asymmetric distribution of hemispheral lesions, in contrast with the symmetric pattern observed in AbLat. The brainstem lesion load was significantly lower in AbEx than in AbLat patients (p = 0.04). Asymmetric abnormalities in blink reflex response excitability in patients with multiple sclerosis are associated with lesser disability and lower tissue loss than abnormalities in response latency. Testing response excitability could

  4. >CME/CNE ARTICLE: Severity Grading in Multiple Sclerosis

    PubMed Central

    Herbert, Joshua; Kister, Ilya

    2016-01-01

    Abstract Currently used classification schemes for multiple sclerosis (MS) have not taken into account disease severity, instead focusing on disease phenotype (ie, relapsing vs. progressive). In this article, we argue that disease severity adds a crucial dimension to the clinical picture and may help guide treatment decisions. We outline a practical, easy-to-implement, and comprehensive scheme for severity grading in MS put forward by our mentor, Professor Joseph Herbert. We believe that severity grading may help to better prognosticate individual disease course, formulate and test rational treatment algorithms, and enhance research efforts in MS. PMID:27803642

  5. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact.

    PubMed

    Rojas, Juan Ignacio; Patrucco, Liliana; Miguez, Jimena; Cristiano, Edgardo

    2016-03-01

    Multiple sclerosis (MS) was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients. PMID:27050854

  6. Scalp fibroma: a rare cutaneous manifestation of tuberous sclerosis

    PubMed Central

    Sharma, Bhawna; Prakash, Swayam; Sannegowda, Raghavendra Bakki; Panagariya, Ashok

    2014-01-01

    We report a case of a 23-year-old woman with a history of generalised tonic–clonic seizures, reddish brown maculopapular swelling over the face and an enlarging swelling over the scalp. Physical examinations revealed angiofibroma of the face and other typical cutaneous lesions of tuberous sclerosis, for example, shagreen patch and periungual fibroma. Scalp swelling was labelled as fibroma by dermatologists, which was further supported by the histopathological findings. Fibroma of the face is one of the commonest lesions, however, fibroma of the scalp is a rarely described entity. PMID:24748136

  7. Epilepsy and multiple sclerosis: Increased risk among progressive forms.

    PubMed

    Martínez-Juárez, Iris E; López-Meza, Elmer; González-Aragón, Maria del Carmen Fernández; Ramírez-Bermúdez, Jesús; Corona, Teresa

    2009-04-01

    Multiple sclerosis (MS) patients are at higher risk for epilepsy. Epilepsy was frequent among our MS patients (6.55%). Progressive MS forms were associated with higher incidence of epilepsy (p=0.021). Partial motor seizures were observed in five patients (62.5%) and generalized tonic-clonic in three (37.5%). Electroencephalogram (EEG) revealed epileptic activity in 62.5%. A high percentage of MS patients with epilepsy (37.5%) reported intoxication as the most severe form of adverse effect of antiepileptic therapy.

  8. [Diabetes insipidus in a pacient with multiple sclerosis].

    PubMed

    Weiler, Fernanda G; Blumberg, Kátia; Liboni, Claudia S; Roque, Eduardo A C; Góis, Aécio F T de

    2008-02-01

    Multiple Sclerosis (ME) is a chronic progressive disease characterized by relapses of demyelination that can occur anywhere in the brain stem, spinal cord and optic nerve. Since central diabetes insipidus (DI) is mainly caused by central nervous system damage (such as trauma, surgery, tumor, infection, sarcoidosis), ME is included among its possible etiologies. However, this association is not commonly described. The clinical suspicion must be made in the presence of polyuria and polydipsia or refractory hypernatremia (in patients without free access to water) during the evolution of ME. We will describe a clinical report in which this association occurred and, after the beginning of desmopressin therapy, the clinical findings were reverted. PMID:18345408

  9. Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis

    PubMed Central

    Turner, Martin R; Benatar, Michael

    2015-01-01

    Multiple candidate biomarkers for amyotrophic lateral sclerosis (ALS) have emerged across a range of platforms. Replication of results, however, has been absent in all but a few cases, and the range of control samples has been limited. If progress toward clinical translation is to continue, the specific biomarker needs of ALS, which differ from those of other neurodegenerative disorders, as well as the challenges inherent to longitudinal ALS biomarker cohorts, must be understood. Appropriate application of multimodal approaches, international collaboration, presymptomatic studies, and biomarker integration into future therapeutic trials are among the essential priorities going forward. PMID:25288265

  10. Optical Coherence Tomography to Assess Neurodegeneration in Multiple Sclerosis.

    PubMed

    Petzold, Axel

    2016-01-01

    Retinal spectral domain optical coherence tomography (OCT) has emerged as a clinical and research tool in multiple sclerosis (MS) and optic neuritis (ON). This chapter summarizes a short OCT protocol as included in international consensus guidelines. The protocol was written for hands-on style such that both clinicians and OCT technicians can make use of it. The protocol is suitable for imaging of the optic nerve head and macular regions as a baseline for follow-up investigations, individual layer segmentation, and diagnostic assessment.

  11. Intrathecal oligoclonal IgG synthesis in multiple sclerosis.

    PubMed

    Petzold, Axel

    2013-09-15

    The diagnosis of multiple sclerosis is based on dissemination in time and space. Before 2010 lack of evidence for dissemination in space could be substituted by a paraclinical test, cerebrospinal fluid (CSF) oligoclonal bands (OCBs). The present meta-analysis (13,467 patients) shows that the diagnostic specificity of OCB drops from 94% to 61% if inflammatory etiologies are considered. Importantly, this was not caused by poor laboratory practice. This review on CSF OCB further illustrates the conceptional problem of substituting dissemination in space with a biomarker. The potential prognostic value of intrathecal OCB will need to be tested prospectively.

  12. Neuro-Ophthalmic Syndromes and Processing Speed in Multiple Sclerosis.

    PubMed

    Costa, Silvana L; Gonçalves, Óscar F; Chiaravalloti, Nancy D; DeLuca, John; Almeida, Jorge

    2016-03-01

    The impact of prior neuro-ophthalmic syndromes on the performance on vision-based neuropsychological tasks in patients with multiple sclerosis (MS) is unknown. Two groups of MS participants, one with (Msos+) and the other without (Msos-), a history of neuro-ophthalmic syndromes, underwent neuropsychological assessment and were compared with healthy age- and education-matched controls (HC). Participants with Msos+ performed significantly worse on the symbol digit modalities test than the Msos- (P < 0.03) and the HC groups (P < 0.01) and coding (P < 0.01). A clinical history of neuro-ophthalmic syndromes is associated with reduced performance on visual processing speed tasks. PMID:26132964

  13. Recent Treatments of Interstitial Lung Disease with Systemic Sclerosis

    PubMed Central

    Yasuoka, Hidekata

    2015-01-01

    Systemic sclerosis (SSc) is a disorder characterized by immune dysfunction, microvascular injury, and fibrosis. Organ involvement in patients with SSc is variable; however, pulmonary involvement occurs in up to 90% of patients with SSc. Interstitial lung disease (ILD) is a major cause of mortality and, thus, a major determinant in the prognosis of patients with SSc. This review summarizes current findings about the characteristics of ILD in patients with SSc, selection of patients with SSc-ILD who are candidates for the treatment, and current treatment options. PMID:26819563

  14. Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis.

    PubMed

    Bedlack, Richard S; Joyce, Nanette; Carter, Gregory T; Paganoni, Sabrina; Karam, Chafic

    2015-11-01

    Given the severity of their illness and lack of effective disease-modifying agents, it is not surprising that most patients with amyotrophic lateral sclerosis (ALS) consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation, and energy healing. This article reviews these in detail. The authors also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy, and shared decision making. Finally, the authors review a program called ALSUntangled, which uses shared decision making to review alternative therapies for ALS. PMID:26515629

  15. Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis.

    PubMed

    Bedlack, Richard S; Joyce, Nanette; Carter, Gregory T; Paganoni, Sabrina; Karam, Chafic

    2015-11-01

    Given the severity of their illness and lack of effective disease-modifying agents, it is not surprising that most patients with amyotrophic lateral sclerosis (ALS) consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation, and energy healing. This article reviews these in detail. The authors also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy, and shared decision making. Finally, the authors review a program called ALSUntangled, which uses shared decision making to review alternative therapies for ALS.

  16. Testing an uncertainty model for women with multiple sclerosis.

    PubMed

    Crigger, N J

    1996-03-01

    This study sought to explain adaptation to the uncertainty of multiple sclerosis (MS) in women. A casual model, developed from the literature and from interviews with four women with MS, was tested on a sample of 90 women with MS. Successful adaptation was measured by self-esteem and mastery. The model accounted for 26% of the variance in mastery, with an empirical model accounting for a higher degree of variance (41%). Findings suggest that the negative impact of uncertainty in women with MS is significantly reduced by their spiritual and social relationships.

  17. The Neurocognitive Profile of the Cerebellum in Multiple Sclerosis

    PubMed Central

    Sarica, Alessia; Cerasa, Antonio; Quattrone, Aldo

    2015-01-01

    In recent years, a high number of studies have demonstrated that neuropsychological functions are altered in multiple sclerosis (MS) patients with cerebellar lesions, mainly including attention, working memory and verbal fluency. Since the present literature is often elusive on this topic, we aim to provide a comprehensive report about the real impact of cerebellar damages (evaluated as volume, lesions or connectivity measures) on cognitive functions. In particular in this review, we report and discuss recent works from 2009 to 2015, which have demonstrated the key role of the cerebellum in cognitive impairment of MS patients. PMID:26030676

  18. Mechanism of Erhuang capsule for treatment of multiple sclerosis.

    PubMed

    Li, Kangning; Fan, Yongping; Yang, Tao; Wang, Lei

    2013-02-25

    Erhuang capsule, a typical formula based on traditional Chinese medicine theory, is widely used to ameliorate multiple sclerosis, inflammation and side effects of glucocorticoid treatment. Oligodendrocyte precursor cells are neural stem cells that are important for myelin repair and regeneration. In the present study, Erhuang capsule effectively improved clinical symptoms and neurological function scores, reduced mortality and promoted recovery of neurological functions of mice with experimental autoimmune encephalomyelitis. The mechanism of action involved significant increases in oligodendrocyte precursor cell proliferation in specific regions of the brain and spinal cord, increased oligodendrocyte lineage gene 2 expression and enhanced oligodendrocyte precursor cell differentiation.

  19. Renal angiomyolipomas, cysts, and cancer in tuberous sclerosis complex.

    PubMed

    Neumann, H P; Schwarzkopf, G; Henske, E P

    1998-12-01

    Tuberous sclerosis is a multisystem syndrome characterized by neurological symptoms and tumors in multiple organs, including kidney, brain, skin, eyes, heart, and lung. The kidney and brain are the two most frequently affected organs in TSC, and renal disease is a leading cause of death in TSC patients. Three types of tumors occur in TSC kidneys: (1) angiomyolipomas, which are benign tumors composed of smooth muscle, fat, and vessels; (2) epithelial cysts; and (3) malignant tumors. This review focuses on the clinical, pathological, and molecular features of these tumors.

  20. Neuro-Ophthalmic Syndromes and Processing Speed in Multiple Sclerosis.

    PubMed

    Costa, Silvana L; Gonçalves, Óscar F; Chiaravalloti, Nancy D; DeLuca, John; Almeida, Jorge

    2016-03-01

    The impact of prior neuro-ophthalmic syndromes on the performance on vision-based neuropsychological tasks in patients with multiple sclerosis (MS) is unknown. Two groups of MS participants, one with (Msos+) and the other without (Msos-), a history of neuro-ophthalmic syndromes, underwent neuropsychological assessment and were compared with healthy age- and education-matched controls (HC). Participants with Msos+ performed significantly worse on the symbol digit modalities test than the Msos- (P < 0.03) and the HC groups (P < 0.01) and coding (P < 0.01). A clinical history of neuro-ophthalmic syndromes is associated with reduced performance on visual processing speed tasks.

  1. [Oral disease modifying therapy of multiple sclerosis: the current view].

    PubMed

    Kappos, L; Boĭko, A N

    2014-01-01

    The review includes data on experimental and clinical studies of new oral methods of multiple sclerosis (MS) disease modifying therapy (DMT). The mechanisms of action, results of clinical trials of stages II and III with the data on their clinical and MRI-efficacy, tolerability and safety of fingolimod, dimethylfumarate (BG-12), teriflunomide and laquinimod are included. The risk management plans for possible side-effects of every product and the peculiarities of their use in individually selected MS treatment are discussed. PMID:24662359

  2. Dimethyl fumarate for relapsing-remitting multiple sclerosis.

    PubMed

    2014-09-01

    For many years the only drugs licensed for the treatment of multiple sclerosis (MS) were administered by injection (interferon beta, glatiramer and ▼natalizumab). Recently, three oral drugs have become available. We have previously reviewed the use of ▼fingolimod for highly active relapsing-remitting MS1 and ▼teriflunomide for the management of relapsing-remitting MS in adults.2 Here, we review the evidence for ▼dimethyl fumarate (Tecfidera-Biogen Idec Ltd) for the treatment of adults with relapsing-remitting MS. PMID:25213591

  3. Teriflunomide: a review of its use in relapsing multiple sclerosis.

    PubMed

    Garnock-Jones, Karly P

    2013-12-01

    Teriflunomide (Aubagio™) is the main active metabolite of leflunomide, an established disease-modifying anti-rheumatic drug. Teriflunomide is an inhibitor of de novo pyrimidine synthesis, reducing lymphocyte proliferation, amongst other immunomodulatory effects; autoimmunity is believed to be one of the potential mechanisms of disease for multiple sclerosis. Teriflunomide is considered cytostatic but not cytotoxic: it does not affect resting or slowly dividing lymphocytes. This article reviews the available pharmacological properties of oral teriflunomide and its clinical efficacy and tolerability in patients with relapsing multiple sclerosis. While both the 7 and the 14 mg/day dosages are discussed, the 7 mg/day dosage is not approved in the EU. Both dosages are approved in the USA. In phase III trials, teriflunomide 7 or 14 mg/day was consistently demonstrated to be more effective than placebo and as effective as interferon beta-1a in the prevention of relapses in patients with relapsing forms of multiple sclerosis; moreover, teriflunomide 14 mg/day was also consistently shown to be more effective than placebo in prevention of disability progression. Teriflunomide was generally well tolerated in these patients. Long-term, extension data were generally similar to those observed in the shorter-term trials. Teriflunomide is associated with increased liver enzyme levels, and is contraindicated in pregnant patients because of a potential risk of teratogenicity. As an oral treatment, it offers an alternative to the traditional, parenteral, disease-modifying therapies; however, further investigation into the efficacy and/or tolerability differences between teriflunomide and other available oral drugs would be of great use in the placement of this drug. At present, given the relatively limited long-term data, it is difficult to draw definite conclusions with regard to safety; however, as teriflunomide is the main active metabolite of leflunomide, long-term safety data

  4. An update of teriflunomide for treatment of multiple sclerosis.

    PubMed

    Oh, Jiwon; O'Connor, Paul W

    2013-01-01

    There are a number of oral agents emerging as potential disease-modifying agents in multiple sclerosis (MS). Among these investigational agents, teriflunomide has shown promise in large, multicenter, phase III clinical trials with respect to safety and efficacy in relapsing MS patients, and is the latest disease-modifying agent approved for use in MS patients in the United States. This review will summarize teriflunomide's historical development, clinical pharmacology, studies in animals, clinical trials, and safety data, and will end with a discussion of the role of teriflunomide in MS in the context of existing treatment options. PMID:23761970

  5. Nature plus nurture: the triggering of multiple sclerosis.

    PubMed

    Wekerle, Hartmut

    2015-01-01

    Recent clinical and experimental studies indicate that multiple sclerosis develops as consequence of a failed interplay between genetic ("nature") and environmental ("nurture") factors. A large number of risk genes favour an autoimmune response against the body's own brain matter. New experimental data indicate that the actual trigger of this attack is however provided by an interaction of brain-specific immune cells with components of the regular commensal gut flora, the intestinal microbiota. This concept opens the way for new therapeutic approaches involving modulation of the microbiota by dietary or antibiotic regimens.

  6. Tuberous Sclerosis and Polycystic Kidney Disease: A Rare Association.

    PubMed

    Das, Shyamashis; Bala, Bapi Lal; Ray, Achintya Narayan; Sherpa, Pasang Lahmu; Kumar, Rajiv Ranjan

    2015-04-01

    Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are two different genetic diseases. Although these two diseases are associated very rarely, the association is well recognized. This occurs due to a large deletion involving both PKD-1 and TSC-2 genes on chromosome 16. This is also known as TSC-2/PKD-1 contiguous gene syndrome. We report a 26-year-old female patient with TSC who presented with severe metabolic acidosis due to renal failure. She had palpable enlarged kidneys bilaterally. CT scan of abdomen revealed bilateral enlarged lobulated kidneys studded with multiple cysts which was consistent with the diagnosis of ADPKD. PMID:26591174

  7. Mitochondrial dysfunction in amyotrophic lateral sclerosis - a valid pharmacological target?

    PubMed

    Muyderman, H; Chen, T

    2014-04-01

    Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by the selective death of upper and lower motor neurons which ultimately leads to paralysis and ultimately death. Pathological changes in ALS are closely associated with pronounced and progressive changes in mitochondrial morphology, bioenergetics and calcium homeostasis. Converging evidence suggests that impaired mitochondrial function could be pivotal in the rapid neurodegeneration of this condition. In this review, we provide an update of recent advances in understanding mitochondrial biology in the pathogenesis of ALS and highlight the therapeutic value of pharmacologically targeting mitochondrial biology to slow disease progression.

  8. Frontotemporal Dysfunction and Dementia in Amyotrophic Lateral Sclerosis.

    PubMed

    Woolley, Susan C; Strong, Michael J

    2015-11-01

    Although amyotrophic lateral sclerosis (ALS) is classically considered a disorder exclusively affecting motor neurons, there is substantial clinical, neuroimaging, and neuropathologic evidence that more than half of patients have an associated syndrome of frontotemporal dysfunction. These syndromes range from frontotemporal dementia to behavioral or cognitive syndromes. Neuroimaging and neuropathologic findings are consistent with frontotemporal lobar degeneration that underpins alterations in network connectivity. Future clinical trials need to be stratified based on the presence or absence of frontotemporal dysfunction on the disease course of ALS. PMID:26515622

  9. Tuberous sclerosis with oral manifestations: A rare case report

    PubMed Central

    Sodhi, SPS; Dang, Ramandeep Singh; Brar, Gursimrat

    2016-01-01

    Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome, inherited as an autosomal dominant trait with a high incidence of sporadic cases and protean clinical expression, with a incidence of prevalence between 1 in 10,000 and 1 in 170,000. The cardinal features of TSC are skin lesions, convulsive seizures, and mental retardation. We report a sporadically occurring case of definite TSC in a young female who presented with oral and cutaneous manifestations without mental retardation or history of convulsive seizures, which to the best of our knowledge has not been reported so far. PMID:26958526

  10. Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis.

    PubMed

    Motegi, Sei-Ichiro; Toki, Sayaka; Yamada, Kazuya; Uchiyama, Akihiko; Ishikawa, Osamu

    2014-11-01

    Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of cardiovascular diseases, including carotid, coronary and peripheral arterial disease (PAD). The association of plasma homocysteine levels with peripheral vascular involvements, such as Raynaud phenomenon (RP), digital ulcers (DU) in systemic sclerosis (SSc) patients has not been well studied. The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with SSc. Plasma homocysteine levels in 151 Japanese patients with SSc and 20 healthy controls were examined. No significant differences were observed in plasma homocysteine levels between SSc patients and healthy individuals. Demographic and clinical features of the SSc patients revealed that severe skin sclerosis, anti-topoisomerase I antibody positivity, complications of DU, acro-osteolysis (AO) and interstitial lung disease (ILD) were significantly more prevalent among the patients with elevated plasma homocysteine levels. The plasma homocysteine levels were positively correlated with modified Rodnan total skin score. The plasma homocysteine levels in the SSc patients with DU, AO and ILD were significantly higher than those in the SSc without DU, AO and ILD, respectively. Plasma homocysteine levels did not correlate with either the mean or max intima-media thickness (IMT) or plaque score, suggesting that plasma homocysteine levels might not be associated with carotid artery atherosclerosis in SSc patients. The measurement of plasma homocysteine levels in SSc patients might be useful for the risk stratifications of severe skin sclerosis, DU and AO.

  11. Amyotrophic Lateral Sclerosis Regional Variants (Brachial Amyotrophic Diplegia, Leg Amyotrophic Diplegia, and Isolated Bulbar Amyotrophic Lateral Sclerosis).

    PubMed

    Jawdat, Omar; Statland, Jeffrey M; Barohn, Richard J; Katz, Jonathan S; Dimachkie, Mazen M

    2015-11-01

    Amyotrophic lateral sclerosis (ALS), a rapidly progressive, invariably fatal disease, involves mixed upper and lower motor neurons in different spinal cord regions. Patients with bulbar onset progress more rapidly than patients with limb onset or with a lower motor neuron presentation. Recent descriptions of regional variants suggest some patients have ALS isolated to a single spinal region for many years, including brachial amyotrophic diplegia, leg amyotrophic diplegia, and isolated bulbar palsy. Clearer definitions of regional variants will have implications for prognosis, understanding the pathophysiology of ALS, identifying genetic factors related to slower disease progression, and future planning of clinical trials.

  12. Nodular Scleroderma Revisited: Systemic Sclerosis Presenting as Annular Keloidal Sclerotic Plaques

    PubMed Central

    Lortscher, David N.; Cohen, Philip R.; Bangert, Carolyn A.

    2016-01-01

    Background: Nodular scleroderma, also known as keloidal scleroderma, is a rare variant of systemic sclerosis. Purpose: The clinical features, pathologic findings and postulated pathogenesis of nodular scleroderma are discussed. Methods: A woman with previously undiagnosed systemic sclerosis who presented with nodular scleroderma is described. Using the PubMed database, a literature search was performed on keloidal scleroderma, nodular scleroderma, and systemic sclerosis. Results: Nodular scleroderma is characterized by firm plaques or nodules, which can mimic a keloid, that are typically located on the anterior orposterior upper trunk and the arms; they show pathologic changes of scleroderma, keloid, or hypertrophic scar. Akeloidal response of inflamed skin that is involved in an active fibrotic process inherent to systemic sclerosis, in individuals who are genetically predisposed to keloid formation, is the hypothesized pathogenesis. Conclusion: Nodular scleroderma is rare. The authors’ patient presented with diarrhea, dysphagia, fatigue, Raynaud’s phenomenon, shortness of breath, and annular keloidal plaques of morphea whose biopsy showed features of hypertrophic scar; additional studies confirmed the diagnosis of the nodular scleroderma variant of systemic sclerosis. The possibility of systemic sclerosis should be entertained in patients who present with nodularor keloidal plaques that morphologically resemble morphea and have histologic findings of a scar or a keloid—especially if there are associated symptoms suggestive for systemic sclerosis. PMID:27386053

  13. Regulatory T cell number in multiple sclerosis patients: A meta-analysis.

    PubMed

    Noori-Zadeh, Ali; Mesbah-Namin, Seyed Alireza; Bistoon-Beigloo, Sara; Bakhtiyari, Salar; Abbaszadeh, Hojjat-Allah; Darabi, Shahram; Rajabibazl, Masoumeh; Abdanipour, Alireza

    2016-01-01

    Regulatory T cells (Treg cells), defined as CD4(+) CD25(+) FoxP3(+) T cells by expression of CD4, high-affinity IL-2 receptor and the transcription factor, forkhead box P3 (FoxP3). They play a pivotal role in protecting individuals from autoimmunity and a growing body of evidence suggests their role in the prevention of multiple sclerosis development. However, there are discrepancies about the type of defect in the Treg cells of multiple sclerosis patients and especially whether the Treg number alteration could be contributed to multiple sclerosis pathogenesis. Indeed, whether low number of Treg cells can be a risk factor contributing to multiple sclerosis pathogenesis is the matter of debate and there is not any comprehensive agreement on it. Thus, the objective of this systematic review and meta-analysis was to precisely quantify the nature and magnitude of the association between Treg cell number and the risk ratio/odds ratio (OR) of multiple sclerosis in the case-control studies. Hence, medical databases of Embase, PubMed/Medline, PubMed, PubMed Central and SCOPUS were searched for empirical papers using "Regulatory T cell frequency", "Treg frequency" in combination with "multiple sclerosis". In the case-control studies, papers were reviewed for inclusion/exclusion criteria and 8 publications were included. Under random-effect model meta-analysis the data showed that the frequency of Treg cells was not a risk factor in multiple sclerosis using current laboratory methods.

  14. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis.

    PubMed

    Severin, Mary E; Lee, Priscilla W; Liu, Yue; Selhorst, Amanda J; Gormley, Matthew G; Pei, Wei; Yang, Yuhong; Guerau-de-Arellano, Mireia; Racke, Michael K; Lovett-Racke, Amy E

    2016-06-01

    Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFβ signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFβ signalling components in their naïve CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFβ pathway, resulting in a reduced capacity of naïve CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFβ-targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFβ signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFβ-targeting miRNAs in naïve CD4 T cells of patients with multiple sclerosis impairs TGFβ signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis.

  15. New candidates for CD4 T cell pathogenicity in experimental neuroinflammation and multiple sclerosis.

    PubMed

    Hoppmann, Nicola; Graetz, Christiane; Paterka, Magdalena; Poisa-Beiro, Laura; Larochelle, Catherine; Hasan, Maruf; Lill, Christina M; Zipp, Frauke; Siffrin, Volker

    2015-04-01

    Multiple sclerosis is a chronic autoimmune demyelinating disease of the central nervous system, which is thought to be triggered by environmental factors in genetically susceptible individuals leading to activation of autoreactive T lymphocytes. Large multi-centre genome-wide association studies have identified multiple genetic risk loci in multiple sclerosis. In this study, we investigated T cell transcriptomic changes in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. We correlated these findings with the multiple sclerosis risk genes postulated by the most recent Immunochip analysis and found that multiple sclerosis susceptibility genes were significantly regulated in experimental autoimmune encephalomyelitis. Our data indicate that nine distinct genes associated with multiple sclerosis risk, Bach2, Il2ra, Irf8, Mertk, Odf3b, Plek, Rgs1, Slc30a7 and Thada, can be confirmed to be differentially regulated in pathogenic CD4(+) T cells. During the effector phase within the inflamed CNS, CD4(+) T cells undergo comprehensive transformation and we identified key transcription factors and signalling networks involved in this process. The transformation was linked to metabolic changes with the involvement of liver X receptor/retinoid X receptor signalling and cholesterol biosynthesis, which might control the T cell effector function in the central nervous system. Thus, our study confirms the involvement of multiple sclerosis risk genes in the pathophysiology of the animal model and sheds light on additional disease-relevant inflammatory networks.

  16. Visual Evoked Potentials as a Readout of Cortical Function in Infants With Tuberous Sclerosis Complex.

    PubMed

    Varcin, Kandice J; Nelson, Charles A; Ko, Jordan; Sahin, Mustafa; Wu, Joyce Y; Jeste, Shafali Spurling

    2016-02-01

    Tuberous sclerosis complex is an autosomal dominant genetic disorder that confers a high risk for neurodevelopmental disorders, such as autism spectrum disorder and intellectual disability. Studies have demonstrated specific delays in visual reception skills that may predict the development of autism spectrum disorder and intellectual disability. Based on evidence for alterations in the retinogeniculate pathway in animal models of tuberous sclerosis complex, we asked whether children with tuberous sclerosis complex demonstrate alterations in early visual processing that may undermine the development of higher-level visual behaviors. Pattern-reversal visual evoked potentials were recorded in infants with tuberous sclerosis complex (n = 16) and typically developing infants (n = 18) at 12 months of age. Infants with tuberous sclerosis complex demonstrated remarkably intact visual evoked potentials even within the context of intellectual disability and epilepsy. Infants with tuberous sclerosis complex show intact visual cortical processing, suggesting that delays in visually mediated behaviors in tuberous sclerosis complex may not be rooted in early visual processing deficits.

  17. Tumor necrosis factor alpha gene -376 polymorphism and susceptibility to multiple sclerosis: an Egyptian study.

    PubMed

    Nada, Mona Abd el Fattah; Labib, Dalia Ahmed

    2011-03-01

    Tumor necrosis factor alpha, a proinflammatory cytokine, plays an important role in the clinical activity of relapsing-remitting multiple sclerosis and the development of progression. Dysregulation in the expression of tumor necrosis factor gene had been suggested in the pathogenesis of multiple sclerosis. Our aim was to investigate the relationship between tumor necrosis factor α-376 polymorphism with disease susceptibility and course of multiple sclerosis in Egyptian patients. Polymerase chain reaction and restriction fragment length polymorphism were carried out on 36 primary progressive multiple sclerosis patients, 36 age- and sex-matched remitting relapsing multiple sclerosis patients (diagnosed according to McDonald's Diagnostic criteria) and 30 age- and sex-matched healthy controls. The GG genotype and the guanine allele (G) were detected significantly more often in the primary progressive (p = 0.02; p = 0.004, respectively) and remitting relapsing (p = 0.015; p = 0.024, respectively) multiple sclerosis groups as compared with the healthy control group. The G allele in the examined position in tumor necrosis factor alpha might have a role as regards susceptibility in both remitting relapsing and primary progressive multiple sclerosis.

  18. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

    PubMed Central

    Papaioannou, Andriana I; Zakynthinos, Epaminondas; Kostikas, Konstantinos; Kiropoulos, Theodoros; Koutsokera, Angela; Ziogas, Athanasios; Koutroumpas, Athanasios; Sakkas, Lazaros; Gourgoulianis, Konstantinos I; Daniil, Zoe D

    2009-01-01

    Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis. PMID:19426547

  19. Cognitive status in patients with multiple sclerosis in Lanzarote

    PubMed Central

    Pérez-Martín, María Yaiza; Eguia-del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

    2016-01-01

    Objectives Cognitive impairment is a common feature in multiple sclerosis affecting ~43%–72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. Patients and methods In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Results Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Conclusion Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety. PMID:27418825

  20. Treatment of multiple sclerosis with chinese scalp acupuncture.

    PubMed

    Hao, Jason Jishun; Cheng, Wei; Liu, Ming; Li, He; Lü, Xiaolin; Sun, Zhongren

    2013-01-01

    Chinese scalp acupuncture is a contemporary acupuncture technique with just 40 years of history. It integrates traditional Chinese needling methods with Western medical knowledge of the cerebral cortex and has been proven to be a very effective technique for treating multiple sclerosis (MS) and other central nervous system disorders. A 65-year-old male patient who had had MS for 20 years was treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for six sessions. After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. At this writing, the patient has been in remission for 26 months. This case demonstrates that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient's quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients with multiple sclerosis to remain in remission.