Multiple sclerosis

Author(s):  
Alasdair Coles ◽  
Alastair Compston

The papers in this chapter illustrate the picture that has emerged of multiple sclerosis as an inflammatory disorder of the central nervous system, caused by a complex interplay of multiple genetic susceptibility alleles and unknown environmental triggers. Multiple sclerosis is a disease in which there is first demyelination of nerves, followed by axonal degeneration. Demyelination is caused by inflammation, as shown by the synthesis of immunoglobulins within the CNS, and magnetic resonance imaging has shown that only the minority of inflammatory lesions cause symptoms. All of these discoveries were made in the twentieth century, which ended with the first demonstration that a treatment—interferon-beta—could influence the natural history of the disease.

2019 ◽  
Vol 77 (6) ◽  
pp. 436-441 ◽  
Author(s):  
Renan Barros DOMINGUES ◽  
Gustavo Bruniera Peres FERNANDES ◽  
Fernando Brunale Vilela de Moura LEITE ◽  
Carlos SENNE

ABSTRACT Multiple sclerosis (MS) is an autoimmune, inflammatory, and degenerative disease of the central nervous system. Axonal degeneration is triggered by inflammation and is the pathological substrate of progressive disability in patients with MS. Therapeutic interventions can reduce inflammatory activity, thus delaying neurodegeneration and the progression of disability. Disease activity and neurodegeneration are assessed mainly through clinical evaluation and magnetic resonance imaging. These measures lack sensitivity and accuracy, so new biomarkers are necessary. Several markers have been studied and to date the most promising is neurofilament light (NfL), a component of the axonal cytoskeleton, which is released into cerebrospinal fluid (CSF) following axonal damage. In the present study, we review the current knowledge about CSF NfL determination in MS, clinically isolated syndrome, and radiologically isolated syndrome, and critically discuss how CSF NfL measurement may contribute to therapeutic decision-making in these patients.


2021 ◽  
Vol 16 ◽  
pp. 117727192110133
Author(s):  
Ameneh Jafari ◽  
Amirhesam Babajani ◽  
Mostafa Rezaei-Tavirani

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system (CNS) resulting in demyelination and axonal loss in the brain and spinal cord. The precise pathogenesis and etiology of this complex disease are still a mystery. Despite many studies that have been aimed to identify biomarkers, no protein marker has yet been approved for MS. There is urgently needed for biomarkers, which could clarify pathology, monitor disease progression, response to treatment, and prognosis in MS. Proteomics and metabolomics analysis are powerful tools to identify putative and novel candidate biomarkers. Different human compartments analysis using proteomics, metabolomics, and bioinformatics approaches has generated new information for further clarification of MS pathology, elucidating the mechanisms of the disease, finding new targets, and monitoring treatment response. Overall, omics approaches can develop different therapeutic and diagnostic aspects of complex disorders such as multiple sclerosis, from biomarker discovery to personalized medicine.


2008 ◽  
Vol 14 (3) ◽  
pp. 428-430 ◽  
Author(s):  
JNP Zwemmer ◽  
JCJ Bot ◽  
B. Jelles ◽  
F. Barkhof ◽  
CH Polman

We present three patients with a clinical course and cerebrospinal fluid findings consistent with a diagnosis of primary progressive multiple sclerosis (PPMS). Extensive and repeated magnetic resonance imaging (MRI) examinations showed only diffuse abnormality in brain and spinal cord, but no focal lesions. We propose that these cases represent the most pure form of PPMS, even though according to currently applied criteria this diagnosis can not be made in the absence of focal lesions on MRI. Multiple Sclerosis 2008; 14: 428—430. http://msj.sagepub.com


2020 ◽  
Vol 13 (2) ◽  
pp. 153-172
Author(s):  
Eda Vrtačnik Bokal ◽  
Urban Vrtačnik

Multiple sclerosis (MS) is an autoimmune inflammatory disorder of the central nervous system. It is common in the reproductive period and can lead to infertility and significant disability. The treatment on multiple sclerosis is recently more successful and enables better quality of life, therefore rising hope and desire for future parents, also in terms of successful infertility treatments. In this context, the couples should be managed concerning the detrimental effect of the disease itself on fertility, detrimental effect of the drugs used for treatment on gonads and in terms of the implementation of drugs used for ovarian stimulation and their impact on the basic disease (MS). The article finds solutions on the legal outcomes in situations where infertility treatments may negatively impact the progress of MS, as well as the solutions on how to (successfully) provide infertility treatments to the patients with MS. It proposes interdisciplinary approach between gynaecologists and neurologists to perform required weighing of benefits and risks (burdens), deriving from specific action or treatment, whereas for the patients who shall not undergo infertility treatments due to their medical status, related to MS, it proposes storage of gametes under conditions, set by the law.


2021 ◽  
pp. 62-64
Author(s):  
I. Vanessa Marin Collazo

A 58-year-old, right-handed man with a medical history of nephrolithiasis, essential hypertension, and type 2 diabetes sought care for a 6-year history of gait impairment. Initially, he noted subtle left foot and ankle weakness with associated falls that progressed over time. Two to 3 years later he again noted progressive left leg weakness and new arm weakness. Subsequently, progressive pain developed on the soles of his feet in addition to edema with erythematous discoloration around the left ankle and foot. On neurologic examination, he was found to have mild upper motor neuron pattern weakness in the left arm and leg, most pronounced in the left hand finger extensor and left hip flexion and abduction. Left patellar reflex was brisk, and there was an extensor Babinski sign on the left. There was mild reduction in pinprick sensation in both feet. His gait was spastic with left leg circumduction. Magnetic resonance imaging of the brain showed left-sided predominant periventricular and subcortical T2 fluid-attenuated inversion recovery hyperintensities. Magnetic resonance imaging of the cervical and thoracic spinal cord showed intramedullary cord T2 signal hyperintensities, eccentrically located on the left at C3, C5, C6, on the right at C7 to T1, and centrally at T4/T5 and T8/T9. A diagnosis of primary progressive multiple sclerosis was made. The patient met the 2017 McDonald criteria for primary progressive multiple sclerosis. After the diagnosis was confirmed and comprehensive education about the disease and the role of disease-modifying therapy was discussed with the patient, he was started on ocrelizumab. Gabapentin was started for management of painful foot paresthesias. Vitamin D3 supplementation was started. Physical therapy was also initiated. Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system and is the leading cause of disability in the young population. Approximately 1 million people in the United States currently have multiple sclerosis.


2021 ◽  
pp. 20-21
Author(s):  
Samantha A. Banks ◽  
Eoin P. Flanagan

A 59-year-old White man with a history of excised basal and squamous cell skin cancers was evaluated for gait difficulties. He had erectile dysfunction but no bowel or bladder dysfunction. He also reported fatigue. He began using a cane for ambulation 2 weeks before evaluation at our facility. His medications included vitamin D and sildenafil. He was a lifelong nonsmoker and had no family history of multiple sclerosis. Neurologic examination at the time of our evaluation 3 years after onset was notable for a positive Hoffman sign on the right and mild weakness of the right triceps but preserved strength elsewhere. He had a spastic gait with moderate spasticity in both lower extremities, hyperreflexic patellar and ankle jerks bilaterally, and bilateral positive Babinski sign. The remainder of the examination was essentially normal. Magnetic resonance imaging of the brain showed a single lesion at the cervicomedullary junction and medullary pyramids, more prominent on the right. There was also some accompanying atrophy that was also visible on cervical spine magnetic resonance imaging. Results of cerebrospinal fluid analysis showed a normal white blood cell count, increased protein concentration (108 mg/dL), and positive oligoclonal bands. The progressive nature of his symptoms, spinal fluid results, and lesion appearance were all consistent with a diagnosis of progressive solitary sclerosis. At the time this patient was seen, no immunomodulatory medications for progressive solitary sclerosis were approved, so no immunomodulatory medication was tried. Ongoing symptomatic management was recommended. Progressive solitary sclerosis is a rare variant of multiple sclerosis in which patients have a single central nervous system demyelinating lesion and development of motor progression attributable to that lesion. Patients can initially have a clinical episode followed by progression or can have a progressive course without an initial relapse.


Author(s):  
Teri L. Schreiner ◽  
Jeffrey L. Bennett

Neuromyelitis optica (NMO), or Devic’s disease is an inflammatory disorder of the central nervous system that preferentially affects the optic nerves and spinal cord. Initially considered a variant of multiple sclerosis (MS), NMO is now clearly recognized to have distinct clinical, radiographic, and pathologic characteristics. Historically, the diagnosis of NMO required bilateral optic neuritis and transverse myelitis; however, the identification of a specific biomarker, NMO-IgG, an autoantibody against the aquaporin-4 (AQP4) water channel, has broadened NMO spectrum disease to include patients with diverse clinical and radiographic presentations. This chapter addresses the diagnosis, pathophysiology, and management of the disease.


2012 ◽  
Vol 7 (3) ◽  
pp. 189 ◽  
Author(s):  
Beatriz Moreno ◽  
Pablo Villoslada ◽  
◽  

Multiple sclerosis (MS) is considered to be an autoimmune disease that is caused by the immune system attacking the central nervous system (CNS) leading to myelin loss and axonal damage, resulting in long-term disability. The pathophysiology of MS is complex with involvement of genetic and environmental factors that define the susceptibility to generate the autoimmune attack. In the last decade, several immunomodulatory drugs have been approved, including recombinant proteins such as interferon-beta, monoclonal antibodies such as natalizumab, or small chemicals including glatiramer acetate. In addition, there is a wide pipeline of new immunomodulators finishing Phase II or III trials. However, at present there are no approved treatments that directly reduce nervous system damage or enhance its repair. Novel neuroprotective agents have been identified in pre-clinical studies but their development is being prevented by the absence of appropriate understanding of the mechanisms of CNS damage by inflammation as well as by the lack of clinical platforms to test them. In this review, we describe the different mechanisms of axonal injury and discuss some of the principal therapeutic candidates that could provide neuroprotection in MS.


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