Multiple Sclerosis Pathology Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesions and their relation to the inflammatory process is described.
DOI: 10.1101/cshperspect.a028936 Abstract Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain.
Cortical lesions are common in early MS, where they may even represent the earliest pathologic event in some MS patients and are inflammatory and topographically associated with meningeal inflammation.
Description. Multiple sclerosis is a condition characterized by areas of damage (lesions) on the brain and spinal cord . These lesions are associated with destruction of the covering that protects nerves and promotes the efficient transmission of nerve impulses (the myelin sheath ) and damage to nerve cells.
Multiple sclerosis is caused by your immune system mistakenly attacking the brain and nerves. It's not clear why this happens but it may be a combination of genetic and environmental factors.
Multiple sclerosis may be classified into four groups according to the clinical course of the disease. This includes relapsing-remitting, secondary-progressive, primary-progressive, and progressive-relapsing.
MS appears to involve a complex combination of genetic susceptibility and nongenetic triggers, such as environmental factors, that result in a steady or rapid progression of neurological symptoms. The main characteristics of MS pathology include inflammatory demyelination, axonal injury, and development of CNS lesions.
Between 1 and 2 in every 10 people with the condition start their MS with a gradual worsening of symptoms. In primary progressive MS, symptoms gradually worsen and accumulate over several years, and there are no periods of remission, though people often have periods where their condition appears to stabilise.
Relapsing-remitting MS (RRMS) RRMS – the most common disease course – is characterized by clearly defined attacks of new or increasing neurologic symptoms.
Types of neuromuscular disorders include: Amyotrophic lateral sclerosis (ALS) Charcot-Marie-Tooth disease. Multiple sclerosis.
Although several names described the condition in the first half of the 20th century - disseminated sclerosis, insular sclerosis, polysclerosis - the title of this book helped establish multiple sclerosis as the accepted name in the English speaking world.
Definition of pathophysiology : the physiology of abnormal states specifically : the functional changes that accompany a particular syndrome or disease.
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which leads to the development of focal inflammatory lesions with secondary axonal damage.
Whatever the underlying condition for MS is, it appears that damage is triggered by an unknown soluble factor in the CSF, potentially produced in meningeal areas; this factor can diffuse into the cortical parenchyma and destroy myelin either directly or indirectly through microglia activation.
People with multiple sclerosis (MS) tend to have their first symptoms between the ages of 20 and 40. Usually the symptoms get better, but then they come back. Some come and go, while others linger. No two people have exactly the same symptoms.
Boston, MA – Multiple sclerosis (MS), a progressive disease that affects 2.8 million people worldwide and for which there is no definitive cure, is likely caused by infection with the Epstein-Barr virus (EBV), according to a study led by Harvard T.H. Chan School of Public Health researchers.
Common early signs of multiple sclerosis (MS) include:vision problems.tingling and numbness.pains and spasms.weakness or fatigue.balance problems or dizziness.bladder issues.sexual dysfunction.cognitive problems.
Genetic Factors MS is not an inherited disease, meaning it is not a disease that is passed down from generation to generation. However, in MS there is genetic risk that may be inherited. In the general population, the risk of developing MS is about 1 in 750 - 1000.
Taken together, the pathology of multiple sclerosis consists of two essentially different features – the focal demyelinated plaque and the diffuse global brain injury. Both types of pathology occur on the background of an inflammatory response, dominated by T cells and activated macrophages or microglia.
The hallmark of multiple sclerosis (MS) pathology is the focal demyelinated lesion, or “plaque,” with perivascular inflammatory infiltration and focal blood–brain barrier (BBB) breakdown. Axonopathy is an early and prominent feature of acute MS lesions.
Atrophy (linear, area, or volume loss) measures of the brain or spinal cord are broadly considered to be indicators of the irreversible , destructive pathology of MS. It is important, however, to acknowledge that atrophy does not reflect the consequences of a single pathology, but is a composite measure of the contributions from axonal loss and demyelination ( Simon, 2006a) and also reflects the organization of the tissue matrix, as shown in neuropathology and neuropathology–MRI correlation series. Additionally, atrophy may differentially impact an entire tissue class (e.g., gray matter) more than another (e.g., white matter). Some white-matter structures appear to collapse when injured (e.g., corpus callosum) more than other deep white-matter regions, and are better atrophy indicators ( Simon et al., 1987) ( Fig. 18.4 ). Consequently injury may or may not result in measurable atrophy in specific regions and circumstances ( Simon, 2006a; Shiee et al., 2012 ). Nevertheless, atrophy has become an important biomarker in MS studies, with a generally stronger correlation with clinical disability than that between T2-hyperintense lesion load or other MRI measures and disability (summarized in Fisher, 2011 ). It is clear that brain atrophy occurs early in the course of disease ( Simon, 2012 ), that these changes are measureable over relatively short (generally 1-year) intervals in groups of patients, and there are at least modest clinical and prognostic correlations ( Fisher et al., 2008; Fisher, 2011 ). As a measure of the destructive pathology, atrophy is considered a principal measure for inclusion in trials of neurodegeneration and repair ( Barkhof et al., 2009; Vigeveno et al., 2012 ). Supporting the use of atrophy measures, recent analyses show a relationship between the impact of treatment on brain atrophy and impact on disability progression ( Sormani et al., 2013 ). Brain ( Altmann et al., 2009) and spinal cord atrophy measures are being increasingly incorporated into studies of progressive MS.
The hallmark of MS pathology is the focal demyelinated lesion, or “plaque,” present in the white matter of the optic nerves, brain, and spinal cord. Acute lesions are invariably associated with focal breakdown of the BBB and perivascular inflammatory infiltrates. MS infiltrates are dominated by T cells (with a relatively high CD8/CD4 ratio) and myeloid cells (blood-derived monocytes/macrophages and activated microglia). Macrophages/monocytes and activated microglia are spatially associated with disintegrating myelin sheaths, and they actively take up myelin debris. Apoptosis and loss of oligodendrocytes vary widely among lesions. Frequent sites of lesion formation include subcortical and periventricular cerebral white matter, middle cerebellar peduncles, and the posterior columns of the cervicothoracic spinal cord. In the brain, infiltrates frequently follow the course of pericallosal venules, resulting in “Dawson fingers,” which are oblong lesions oriented perpendicular to the long axes of the lateral ventricles ( Fig. 66.2 ).
White blood cell (WBC) counts tend to be within normal limits or only slightly elevated in the CSF of most patients with MS. Nonetheless, there is growing recognition that low-grade diffuse meningeal inflammation and focal perivascular meningeal inflammation are common. Meningeal inflammation is most prominent in progressive forms of MS but is prevalent in early MS as well. The meningeal infiltrates are topographically associated with cortical lesions. Lymphoid follicle–like structures, composed of proliferating B cells, T cells, and follicular dendritic cells (FDCs), have been observed in the meninges of up to 40% of autopsied brains from individuals with SPMS. 6 In almost every case, the follicles were found to reside in deep sulci and abut an underlying subpial lesion, suggesting that toxic factors are released by inflammatory cells in the follicles and diffuse into the brain parenchyma. The presence of lymphoid follicles has been associated with a more severe clinical course, shorter disease duration, and younger age at death.
Multiple Sclerosis Pathology. Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesions and their relation to the infla ….
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which gives rise to focal lesions in the gray and white matter and to diffuse neurodegeneration in the entire brain. In this review, the spectrum of MS lesions and their relation to the inflammatory process is described.
There are three main clinical manifestations of MS, each with unique initial presenting symptoms: 1 Opticospinal MS: blurred vision, vision changes, memory problems, and lesions on the optic nerve. 2 Spinal MS: weakness, numbness, bladder and bowel problems 3 Cerebellar MS: nystagmus, ataxia and weakness in all extremities
The loss of myelin causes a loss of nerve conductivity and eventual death of neurons. This death of neurons leads to a loss of brain volume and disruption of sodium, calcium and potassium ion channels, which further interfere with neuronal conductivity (McCance & Huether, 2014).
To correctly diagnose the disease there must be evidence of neuronal damage in at least two areas of the CNS, and this damage must have occurred at least one month apart (Garg & Smith, 2015).
The etiology of MS is still unknown, however it is thought that MS is may be brought on by an infection that occurs in an individual who is genetically susceptible. Many environmental factors are also believed to play a role in the development of the disease (McCance & Huether, 2014).
The pathologic hallmark of multiple sclerosis is multiple focal areas of myelin loss within the CNS called plaques or lesions, accompanied by variable gliosis and inflammation and by relative axonal preservation. Active multiple sclerosis lesions are infiltrated by macrophages containing myelin debris.
The pathologic hallmark of MS consists of focal demyelinated plaques within the CNS , with variable degrees of inflammation, gliosis, and neurodegeneration. Active MS lesions show a profound pathologic heterogeneity with four major patterns of immunopathology, suggesting that the targets of injury and mechanisms of demyelination in MS may be different in different disease subgroups. Recent pathologic studies have suggested that the subarachnoid space and cortex may be initial sites and targets of the MS disease process, that inflammatory cortical demyelination is present early in MS, and that meningeal inflammation may drive cortical and white matter injury in some MS patients.
The pathologic hallmark of multiple sclerosis (MS) is multiple focal areas of myelin loss within the CNS called plaques or lesions ( Figure 1-1 A–C). 1,2 Demyelination is accompanied by variable gliosis and inflammation and by relative axonal preservation ( Figure 1-1 D–I). Lesions are disseminated throughout the CNS but have a predilection for optic nerves, subpial spinal cord, brainstem, cerebellum, and juxtacortical and periventricular white matter regions. 1,2 Although MS has historically been considered a disease primarily affecting the CNS white matter, recent pathologic and imaging studies have established that demyelinated lesions are also commonly found in the cortical gray matter of MS patients. 3–6
NMO is an autoimmune astrocytopathy that causes secondary demyelination ( Figure 1-5 B–D). The water channel aquaporin-4 (AQP4), expressed on astrocytes and highly concentrated in the astrocytic foot processes that abut capillaries and pia in the CNS, has been identified as the target antigen in NMO.
The destruction of myelin in pattern I MS may therefore be mediated by toxic factors produced by activated macrophages. Loss of oligodendrocytes is variable at the active lesional border, but numerous oligodendrocytes reappear in the inactive plaque center, and there is a high incidence of remyelinated plaques.
The neurodegeneration in all demyelinated lesions is invariably associated with inflammation , and in chronic inactive lesions from aged patients with long-standing progressive multiple sclerosis where the inflammatory process has died out, the neurodegeneration is also reduced to levels seen in control patients.
Recent pathologic studies have suggested that the subarachnoid space and cortex may be initial sites and targets of the MS disease process, that inflammatory cortical demyelination is present early in MS, and that meningeal inflammation may drive cortical and white matter injury in some MS patients.