eMedicine Specialties > Radiology > Brain/Spine

Brain, Multiple Sclerosis

Author: James A Wilson, MD, MSc, FRCPC, BSc(H), Neurologist and Clinical Neurophysiologist, Oconee Neurology Services
Coauthor(s): Omar Islam, MD, FRCP(C), Assistant Professor of Diagnostic Radiology, Queen's University; Consulting Staff, Department of Diagnostic Radiology, Division of Neuroradiology, Kingston General Hospital
Contributor Information and Disclosures

Updated: Jan 24, 2007

Introduction

Background

Multiple sclerosis (MS) is an inflammatory demyelinating condition of the central nervous system (CNS) that is generally considered to be autoimmune in nature. White matter tracts are affected, including those of the cerebral hemispheres, infratentorium, and spinal cord. MS lesions, known as plaques, may form in CNS white matter in any location; thus, clinical presentations may be diverse. Continuing lesion formation in MS often leads to physical disability and, sometimes, to cognitive decline.

For excellent patient education resources, visit eMedicine's Muscle Disorders Center. Also, see eMedicine's patient education article, Multiple Sclerosis.

Pathophysiology

As with other autoimmune conditions, in patients with MS, the immune system is triggered to attack its host, possibly as a result of exposure to a molecular sequence that mimics the molecular sequence found in the host tissue. In patients with MS, the immune trigger is unknown, but the targets are myelinated CNS tracts. In regions of inflammation, breakdown of the blood-brain barrier occurs, with perivascular lymphocytic and monocytic infiltration. Focal destruction of myelin ensues, with axonal damage, gliosis, and the formation of sclerotic plaques. Gradually, cumulative damage results in significant loss of white matter and a reduction in total brain volume.

Frequency

United States

The frequency of MS varies depending on both the population and the geographic location. MS is most prevalent in white persons of northern European descent and in persons living in temperate climates. This observation suggests that both genetic and environmental factors influence the frequency of MS.

In the United States, Anderson et al estimated a prevalence of approximately 250,000-350,000 cases in 1990 (Anderson, 1992). With a total population of approximately 250 million, this figure corresponds to a prevalence of approximately 1 case per 1000 population, which is half the prevalence of MS in northern Europe (2 cases per 1000 population). Americans of Japanese descent have a prevalence approximately one quarter that of white Americans, whereas Americans of African descent have approximately one third the prevalence of white Americans.

International

The highest prevalence of MS occurs in the Orkney Islands of Scotland at a rate of 250 cases per 100,000 population (Hauser, 1994). A rate of only 2 cases per 100,000 population is observed in Japan, and MS is exceedingly rare in Africa. However, Americans of Japanese descent have a prevalence approximately one quarter that of white Americans, whereas Americans of African descent have about one third the prevalence of white Americans. These figures suggest an environmental effect and genetic susceptibility.

Mortality/Morbidity

MS is the leading cause of neurologic disability in early-to-middle adulthood, second only to trauma. Thus, the lifelong cumulative disability burden of MS is enormous. Practically any neurologic function can be affected during the course of MS.

• The presence of sensory and motor dysfunction is almost ubiquitous in patients with MS, and visual loss resulting from optic neuritis is not uncommon. Estimates indicate that 15 years after the onset of disease, 50% of persons with MS require ambulatory assistance.
• Cognitive impairment is observed in approximately 43% of individuals with MS (Rao, 1991).
• Litwiller et al reported that more than 80% of MS patients have lower genitourinary tract dysfunction, which may range from bladder and urethral dysfunction to impotence (Litwiller, 1999).

Race

MS is most prevalent in white persons of northern European descent (Hauser, 1994).

Sex

Male-to-female ratio is approximately 1:2 (Noseworthy, 2000).

Age

MS is a disease of early adulthood.

• Onset has been documented in patients aged 2-74 years, although the disease usually appears between the late teenage years and the fourth decade of life, peaking at approximately age 35 years.
• In men, the onset is slightly later than in women (Hauser, 1994).

Anatomy

MS is a demyelinating CNS disorder, and it may affect any central white matter. Lesions are commonly located in the optic nerves and tracts, throughout the supratentorial and infratentorial white matter, and along the myelinated tracts of the spinal cord. Locations may include the corpus callosum, cerebellar white matter, and corticospinal tracts.

Presentation

Clinical diagnosis

A diagnosis of MS is made on the basis of clinical findings by using supporting evidence from ancillary tests such as cerebrospinal fluid (CSF) examination for oligoclonal banding and MRI.

Clinically, MS has historically been diagnosed with the demonstration of white matter dysfunction disseminated in time and space (Schumacher, 1965). With the advent of diagnostic laboratory investigations and imaging techniques, the Poser criteria (Poser, 1983) were proposed to establish a degree of certainty of diagnosis in the absence of the 2 clinical attacks by using terms such as possible MS and probable MS.

Even more recently, with increasing treatment options for MS, and better imaging techniques, newer diagnostic criteria have been suggested that allow diagnosis after a single attack coupled with appropriate positive test results. These criteria have been coined the MacDonald criteria (MacDonald, 2001). Essentially, they allow for the second attack in time to be defined by a new lesion appearing on MRI. Also, the MacDonald criteria allow the dissemination in space to be established on the basis of either 9 typical white matter lesions on MRI or 1 enhancing lesion. If CSF studies show increased immunoglobulin G (IgG) values or oligoclonal banding, the presence of only 2 typical MRI lesions satisfy the dissemination-in-time criteria.

With respect to the initial clinical presentation in MS, it may vary with the white matter tract involved, and it may include somatic sensory changes, optic neuritis, or weakness, to mention just a few possible neurologic presentations. After only a single attack, the diagnosis of MS is suggested if the first impairment is coupled with positive paraclinical test results, such as those on imaging or CSF studies. Furthermore, the attack must be compatible with the pattern of impairment found in patients with MS, which typically means that the duration of deficit is days to weeks. Worsening of vision due to optic neuritis and subsequent exercise is known as the Uhthoff phenomenon.

Clinical course

The clinical course of MS can follow different patterns, and this observation has led to the classification of distinct types of MS. The most common form of MS is termed relapsing-remitting MS, in which progression involves symptoms of neurologic dysfunction frequently followed by partial or complete clinical recovery. In relapsing-remitting MS, global clinical deterioration has traditionally been attributed to cumulative deficit due to incomplete recovery from repeated occurrences of individual relapses. Recently, however, this cumulative deficit has been questioned, because evidence increasingly suggests an ongoing background neurologic deterioration that is independent of the relapses.

Occasionally, the course of MS may be more indolent and exhibit a chronic persistent neurologic deficit without apparent ongoing deterioration or further impairment. Sometimes, this course of MS is called inactive or benign MS, and this form is often observed in patients with prior relapsing-remitting disease.

Another potentially complicating matter clinically is that highly active MS lesions may sometimes demonstrate significant mass effect. Rarely, mass effect can lead to midline shift, herniations, infarctions, and even death. Such a drastic clinical and radiological presentation can lead to an incorrect preliminary diagnosis and inappropriate neurosurgical intervention. When MS presents in a more fulminant, aggressive manner, it is frequently known as malignant MS or the Marburg variant.

See Multiple Sclerosis for a detailed discussion of the clinical aspects of MS.

Preferred Examination

Radiologically, the use of MRI is revolutionizing the investigation, diagnosis, and even the treatment of MS. Usually, MRI is the only imaging modality needed for imaging patients with MS, and it far surpasses all other tests with respect to its positive predictive value.

CSF analysis for oligoclonal banding or IgG levels is no longer routine in the investigation of MS, although this test may be of use when MRI is unavailable or MRI findings are nondiagnostic.

Limitations of Techniques

MRI is useful in the diagnosis of MS and in the treatment of patients. One of the limitations of using MRI in patients with MS is the discordance occurring between lesion location and the clinical presentation. In addition, depending on the number and location of findings, MRI can vary greatly in terms of sensitivity and specificity in the diagnosis of MS.

This is especially true of primary progressive MS, which may not show the classic discrete lesions of relapsing-remitting MS. A clinician presented with an MRI report that details a few "nonspecific white matter lesions" that are "compatible with MS" is often frustrated with the lack of sensitivity and specificity of such a description.

For this reason, imaging findings need to be described in detail, and preferably referenced to one of the published set of diagnostic criteria such as those by Paty or Barkhof (see the CAT Scan and MRI sections below). Finally, the specific patient's neurological history and clinical findings must be correlated with the imaging to establish an accurate diagnosis.

Differential Diagnoses

Brain, Stroke
Optic Neuritis
Progressive Multifocal Leukodystrophy

Other Problems to Be Considered

Acute demyelinating encephalomyelitis
Acute disseminated encephalomyelitis
Atypical facial pain
Brainstem gliomas
Central pontine myelinolysis
Essential tremor
CNS complications (related to opportunistic infections, opportunistic neoplasms, vacuolar myelopathy, and encephalopathy due to HIV)
AIDS-dementia complex
Hemifacial spasm
Inherited metabolic disorders
Lyme disease
Lysosomal storage disease
Metabolic disease and stroke
Myokymia
Paraneoplastic encephalomyelitis
Primary CNS lymphoma
Primary lateral sclerosis
Spinal cord infarction
Sudden visual loss
Neuromyelitis optica (Devic disease)
Diffuse cerebral sclerosis of Schilder (encephalitis periaxialis diffusa)
Concentric sclerosis of Balo

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