MRI Studies

MRI reveals that axonal loss in MS lesions correlates with the presence of permanent Tl-weighted black holes'' on MRI (87-90), a reduction in N-acetyl aspartate (NAA) on magnetic resonance spectroscopy (MRS) (91,92) and the extent of CNS atrophy in the spinal cord (93). Since these imaging parameters correlate with clinical disability, axonal damage likely contributes to irreversible clinical disability in MS. New Gd enhancing lesions mainly occur during the early relapsing phase of the...

Mri In Monitoring Treatment Efficacy In Ms Trials

CMRI-derived end-points have been used as primary and secondary outcome measures for monitoring MS clinical trials (Table 4) (3,4,238-240). In this context, the Average lesion MD (103 mm2 sec) NABT MD (103 mm2 sec) r 0.88, P< 0.001 r 0.81, P< 0.001 Figure 17 (A) Scatterplot of the correlation between the relative activation of the contralateral primary sensorimotor cortex and average lesion mean diffusivity in nondisabled relap-sing-remitting multiple sclerosis patients during a simple...

Balo Concentric Sclerosis BCS

Considered a variant of inflammatory demyelinating disease closely related to MS, BCS is characterized pathologically by large demyelinating lesions with a peculiar pattern of alternating layers of preserved and destroyed myelin, mimicking the rings of a tree trunk (Figure 12). Clinically, BCS resembles Marburg MS with similar acute fulminant onset followed by rapid progression to major disability and death within months (138,141,142). Of interest, one of the cases in Marburg's original series...

Course

Lublin and Reingold (174), after polling many MS experts, defined four temporal patterns. In most patients (80-85 ), the disease initially follows a relapsing pattern of acute exacerbations (attacks) punctuated, usually after some improvement, by periods of stability (remissions). This form of disease, in which the baseline is stationary between attacks, is referred to as relapsing-remitting MS.'' Approximately, 10 to 15 of patients never manifest acute...

Marburg MS

The Marburg variant of MS, recognized as a fulminant and lethal subtype of multiple sclerosis by Otto Marburg in 1906 (138), is characterized by rapid progression and an exceptional severity. The course is generally monophasic and relentlessly progressive, with death consequent to brainstem involvement or mass effect with herniation. Peripheral nervous system involvement may also occur in this variant of MS. Pathologically, the lesions are more destructive than typical MS and characterized by a...

Bladder Bowel and Sexual Disturbances

Disturbances of defecation and especially micturition are among the most disabling features of MS, occurring in up to 78 during the course of the illness (134). Patients may complain of urinary frequency, urgency, and incontinence. Alternatively, the urge to urinate may be accompanied by an inability to voluntarily initiate urine flow. History alone is an unreliable indicator of the physiological status of micturition and must be supplemented by further investigation (135,136). Usually, this...

Pathological Studies

Although the MS lesion includes both inflammatory and demyelinating components, their relative influence on axonal loss is unclear. Classical neuropathologic descriptions of Charcot (1880), Marburg (1906), and Doinikow (1915) recognized degeneration of axons in MS lesions, but emphasized the primary demyelinating nature of the disease (105). More recent studies have demonstrated a high incidence of acute axonal injury within both chronic and early MS lesions (106-108), although the extent of...

Late Remyelination

Remyelination in chronic lesions may be restricted to the plaque edge or may extend throughout the lesion (Figure 7). Such lesions, referred to as shadow plaques, consist of sharply demarcated areas of complete remyelination, and are characterized by reduced staining of myelin (myelin pallor) due to a decreased ratio between myelin Figure 7 (See color insert.) Remyelination in chronic multiple sclerosis is characterized by the reduced staining intensity of myelin and may be restricted to the...

Susceptibility Linkage

It has long been recognized that, despite living at geographical latitudes where multiple sclerosis (MS) is common, genetically isolated ethnic groups including Gypsies in Hungary (1) Indians and Orientals in North America (2) Aborigines in Australia (3) and Maoris in New Zealand (4) remain resistant to the disease. Systematic analysis of familial aggregation of MS in particular, studies of twins (5-8), adoptees (9), and half-siblings (10) has also confirmed Eichhorst's description from the...

Oligodendrocyte Pathology and Early Remyelination

Remyelination

Oligodendrocytes are susceptible to damage via a number of immune or toxic mechanisms present within the MS lesion. These include cytokines such as TNF-a (38), reactive oxygen or nitrogen species, excitatory amino acids such as glutamate (39), complement components, proteolytic and lipolytic enzymes, T-cell mediated injury via T-cell products (perforin lymphotoxin) (40), the interaction of Fas antigen with Fas-ligand (41), CD8+ class I MHC-mediated cytotoxicity (42), or persistent viral...

Fatigue and Sleep

Fatigue is one of the three most frequently disabling symptoms of MS (129) and may be considered abnormal in as many as 78 of patients (130,131). A particular feeling of enervation, severe enough to prevent a patient from carrying out duties and responsibilities or to interfere with work, family, or social life, occurs (132). This specific, but poorly understood, type of fatigue in MS must be distinguished from symptoms of depression, medication side effects, consequences of other medical...

Ms

Progression index time to EDSS 6.0, time to secondary-progressive phase Normalized brain volume and T2-weighted lesion load on MRI Changes in brain volume and in Tl- and T2-weighted lesion loads on MRI Raw EDSS progression index EDSS extent of demyelination and brain atrophy on MRI Progression index time to EDSS 6.0 lesion loads and brain volume on MRI Progression index s2 associated with less severe disease No in women More pronounced brain damage in Yes s4 carriers (even in earliest disease...

Epidemiology

One of the major clues to MS etiology comes from analysis of the remarkable worldwide pattern of MS. This shows a crude but inconsistent north-south gradient in North America and Europe a lower prevalence in most of Asia, Africa, and South America (although many of these studies are less than definitive because of uncertainty about the completeness of case ascertainment) and a reverse south-north gradient in Australia and New Zealand (Chapters 1 and 2). This nonrandom pattern is different from...

Candidate Agents In Ms

It is conceivable that multiple infectious agents trigger MS. Unfortunately, if MS is caused by multiple agents, it is unlikely that measures will be available in the short term to decrease MS risk (14). Another possibility is that classic MS is primarily caused by a known or as yet unidentified agent that has not yet been firmly linked to MS. In favor of the unitary hypothesis is the distinct worldwide distribution of MS, restricted age-specific incidence, the effect of migration on MS risk,...

Persistent Infection

The direct infection hypothesis implies that the virus persists in the brain or perhaps in other organs, periodically seeding the brain. There are many examples of persistent infections or viral latency in the nervous system. In the former category are measles virus (SSPE), HIV, HTLV-1, papovavirus, and rubella virus encephalopathies. Herpes simplex, herpes zoster, EBV, certain retroviruses, and human herpes virus 6 (HHV-6) are examples of common viruses that persist in neural or other tissue,...

Cognitive and Psychiatric Disturbances

In recent years, awareness of cognitive dysfunction in MS patients has increased, although abnormalities have been variably reported in 0 to 90 of cases (104,105). A follow-up study of 45 patients with MS, initially studied early in their disease course, found that only 20 of 37 initially cognitively normal individuals remained so after 10 years (106). Clearly, severe dementia is unusual in MS, but more subtle abnormalities of cognitive function are common. These are often unnoticed by...

Perivenous Encephalomyelitis

Included under the term perivenous encephalomyelitis are several disorders, including ADEM, postinfectious encephalomyelitis, postvaccinial encephalomyelitis, and the most severe hyperacute variant, acute hemorrhagic leukoencephalomyelitis (Hurst disease) (137,152). ADEM is generally a rare, monophasic, typically nonfatal disorder, most often associated with antecedent illness and is a nonspecific respiratory infection. Some fatal cases have followed measles and smallpox vaccination. In...

Hhv6

HHV-6, a recently discovered DNA virus, causes exanthem subitum (roseola) in children. Two variants of HHV-6, A and B have been described. HHV-6B causes most human infections whereas no specific human disorder has been linked to HHV-6A. HHV-6 typically causes rash and fever in children but, in addition, this virus commonly enters the CNS during acute primary infections, occasionally resulting in meningitis or other neurological complications (4,113-115). HHV-6 has also been reported to cause...

Visual Pathway Symptoms

Optic neuritis is one of the most common manifestations of MS, occurring in 14 to 23 of cases (36-39). Patients usually complain of dimming of vision unilaterally, generally accompanied by photophobia and pain aggravated by eye movement. Examination reveals diminished visual acuity of varying severity, and detailed visual field evaluation frequently shows a central scotoma (84). Visual loss is seldom total, and good recovery of vision usually occurs within six months, even when the initial...

Paroxysmal Symptoms

Although some studies report an increased prevalence of epileptic seizures compared to the general population, a recent population-based epidemiologic report from Olmsted County, Minnesota found the occurrence to be similar in MS patients and the general population (147). Recently, five patients were described who had jux-tacortical lesions in the temporal region and presented with temporal lobe epilepsy as the sole manifestation of MS (148). In contrast to true epilepsy, many MS patients...

Diagnosis

The basis for the diagnosis of MS stems from the seminal clinicopathological observations of Charcot (3) and requires the demonstration of lesions disseminated over time and involving multiple, discrete anatomical loci in the white matter of the CNS. Schumacher et al. (4) proposed perhaps the first widely used scheme for the clinical diagnosis of MS in 1965, and all subsequent criteria have been based on these fundamental principles. Schumacher categorized patients as clinically definite,...

The Role Of Mri In The Diagnosis And Prognosis Of Ms

Meningitis Mri Images

The diagnosis of MS is based on the demonstration of disease dissemination in space and time, which can be obtained on a clinical ground (i.e., two relapses in at least two different sites of the CNS) or, alternatively, on the combination of data obtained from clinical assessment and paraclinical and laboratory tests including MRI, cerebrosp-inal fluid (CSF) analysis, and evoked potentials (EP) (33,34). Due to its exquisite sensitivity for the detection of MS lesions at any stage of their...

Info

MS epidemiology worldwide one view of current status. Acta Neurol Scand Suppl 1995 161 23-33. Riise T, Gronning M, Klauber MR, et al. Clustering of residence of multiple sclerosis patients at age 13 to 20 years in Hordaland, Norway. Am J Epidemiol 1991 133 932-939. Munch M, Hvas J, Christensen T, et al. A single subtype of Epstein Barr virus in members of multiple sclerosis clusters. Acta Neurol Scand 1998 98 395-399. MacGregor HS, Latiwonk QI. Is multiple sclerosis an autoimmune...

The Role Of Mri In Understanding Ms Pathophysiology

Tcuadro Clinico Tumores Cerebrales

CMRI is not only important for diagnosing MS but also in giving clues about MS pathophysiology, as outlined by the following findings 1. The patterns of MRI activity vary significantly in individual patients over time, from one patient to another, and across the different clinical pheno-types of MS. Disease activity tends to decline with patients' age (105) and is very low in patients with PPMS (106,107). 2. The harvest of enhancing MS lesions can be markedly increased when administering a TD...

Introduction

Multiple sclerosis (MS) is the most common chronic inflammatory-demyelinating disease affecting the central nervous system (CNS) of young adults in the western countries, leading, in the majority of cases, to severe and irreversible clinical disability (1). Since its clinical introduction, conventional magnetic resonance imaging (cMRI-dual-echo and postcontrast Tl-weighted scans) has greatly improved our ability to diagnose MS and to monitor its evolution, either natural or modified by...

The Active MS Lesion

Luxol Glioblastoma

On gross inspection, the active MS plaque appears as a cheesy soft area of irregular pink or gray color. Microscopically, active inflammatory demyelination is characterized by an intimate admixture of lipid-laden macrophages and large reactive astro-cytes, accompanied by variable perivascular inflammation. The involved areas demonstrate marked pallor of myelin staining with relative preservation of axons, although where damage is most severe, axons may be lost or fragmented and display...

References

The prevalence of multiple sclerosis in the world an update. Neurol Sci 2001 22(2) 117-139. 2. Jersild C, Fog T, Hansen GS, et al. Histocompatibility determinants in multiple sclerosis, with special reference to clinical course. Lancet 1973 2(7840) 1221-1225. 3. Ebers GC, Sadovnick AD, Risen NJ. Canadian Collaborative Study Group. A genetic basis for familial aggregation in multiple sclerosis. Nature 1995 377(6545) 150-151. 4. Sadovnick AD, Armstrong H, Rice G, et al. A...

Humoral Immunity As Indirect Evidence For Autoimmunity In Ms

The humoral arm of the immune system has been implicated in the pathogenesis of MS. The findings of oligoclonal bands (OCBs) and increased levels of intrathecal immunoglobulins (Igs) in more than 90 of MS patients strongly suggest involvement of B-cells in MS. The Igs found in MS CSF include IgG, IgA, IgM, and IgD (92). B-cells, plasma cells, and Ig are typically present in MS lesions, and at times have been identified in normal-appearing white matter of MS patients (93,94). Even in the very...

Brief Review Of Basic Aspects Of Nonconventional Mr Techniques

Magnetisation Transfer Weighted Images

MT MRI is based on the interactions between protons in a relatively free environment and those where motion is restricted. Off-resonance irradiation is applied, which saturates the magnetization of the less mobile protons, but this is transferred to the mobile protons, thus reducing the signal intensity from the observable magnetization. Thus, a low MT ratio (MTR) indicates a reduced capacity of the macromol-ecules in the CNS to exchange magnetization with the surrounding water molecules,...

Somatosensory Symptoms

Sensory complaints are frequent among the earliest symptoms of MS with a recent survey indicating that they were the first manifestation in 43 of patients, but this figure may have included visual as well as somatosensory phenomena (47). The symptoms are often perplexing for the clinician, especially during the onset bout, because they are frequently unassociated with objective signs on the neurological examination. In addition, the anatomical distribution is often peculiar, not corresponding...

Neuromyelitis Optica Devic Disease

Neuromyelitis Optica

NMO is an idiopathic inflammatory CNS demyelinating disease characterized by either monophasic or relapsing attacks of optic neuritis and myelitis. Pathologically, NMO lesions demonstrate extensive demyelination across multiple spinal cord levels, associated with necrosis and cavitation, as well as acute axonal damage in both gray and white matter. There is a pronounced loss of oligodendrocytes within the lesions, and inflammatory infiltrates are comprised of large numbers of macrophages...

The Chronic Inactive MS Lesion

Multiple Sclerosis Lesions

The MS lesion may evolve differently during early and chronic phases of the disease. Different stages and types of demyelinating activity can be identified within these phases. Most neuropathological studies of MS are based on tissue from individuals with long-standing disease. Pathologically, these late chronic cases are characterized by the presence of multiple sharply demarcated plaques of demyelination typically ranging from lt 1 mm to several centimeters in size. Plaques are present in...

Types of MS Lesions

Lesion Medicale

On the basis of topographical distribution of macrophages, and the type of myelin degradation products present within the macrophage, four types of MS plaques can be distinguished Figure 4 . The acute active plaque'' is characterized by the presence of macrophages containing early and late myelin degradation products, distributed throughout the extent of the lesion. The radially expanding ''active rim'' shows the accumulation of numerous macrophages, containing both early and late myelin...

Stages of Demyelinating Activity

Although criteria for the pathological staging of MS lesions are controversial, in order to draw conclusions regarding the earliest events in the development of the MS lesion, it is critical that a precise definition for demyelinating activity be used. Some investigators rely on markers of inflammation to stage lesions based on the extent of perivascular or parenchymal inflammatory cell infiltration 5 , the increased expression of histocompatibility antigens 6 , or adhesion molecules 7,8 , and...