Introductory remarks Multiple sclerosis is a chronic condition, typically characterized by episodes (attacks) of focal disorders of the optic nerves, spinal cord, and brain, which remit to a varying extent, recur over a period of many years, usually leading to progressive deficits. The neurologic manifestations are determined by the varied location and extent of the demyelinating foci. Nevertheless, the lesions have a predilection for certain parts of the CNS, resulting in complexes of symptoms and signs and imaging appearances that can often be recognized as distinctive of MS as discussed in detail in the following text.
Typical features of MS, both in acute attacks and as static remnants of these attacks, include weakness, paraparesis, paresthesias, loss of vision, diplopia, nystagmus, dysarthria, tremor, ataxia, impairment of deep sensation, and bladder dysfunction. The diagnosis may be uncertain clinically at the onset and in the early years of the disease, when symptoms and signs point to a lesion in only one locus of the nervous system. Later, as the disease recurs and disseminates throughout the CNS, the diagnosis becomes more certain. There may be a long period of latency (1 to 10 years or longer) between a minor initial symptom, which may not even come to medical attention, and the subsequent development of more characteristic symptoms. In most cases, there is initially a relapsing-remitting pattern, that is, the signs and symptoms improve partially or completely, followed after a variable interval by the recurrence of the same abnormalities or the appearance of new ones in other parts of the nervous system. Frequently, an initially relapsing profile becomes steadily progressive in later stages of the disease (secondary progressive MS) and in a minority of patients, especially those more than 40 years of age at the time of onset, the disease has a steadily progressive course from its initial presentation (primary progressive MS).
A rule that had in the past guided clinicians is that the diagnosis of MS was not secure unless there was a history of remission and relapse and evidence on examination of more than one discrete lesion of the CNS, summarized as lesions that are “separated in time and space.” The advent of MRI and its capacity to identify clinically inevident lesions and lesions of different ages has replaced the exclusive dependence on clinical criteria for the diagnosis.
Before being sectioned, the brain and spinal cord generally show no evidence of disease, but the surface of the spinal cord may appear and feel uneven. Sectioning of the brain and cord discloses numerous scattered patches where the tissue is slightly depressed below the cut surface and stands out from the surrounding white matter by virtue of its pink-gray color (a result of loss of myelin). The lesions may vary in diameter from less than a millimeter to several centimeters; they principally affect the white matter of the brain and spinal cord, and do not extend beyond the root entry zones of the cranial and spinal nerves. It is because of their sharp delineation that they were called plaques by French pathologists. Almost all the pathologic features currently portrayed as novel findings were described by Adams and Kubik over a half century ago.
The topography of the lesions is noteworthy. A periventricular localization is characteristic, but only where subependymal veins line the ventricles (mainly adjacent to the bodies and atria of the lateral ventricles). Other favored structures are the optic nerves and chiasm (but rarely the optic tracts) and the spinal cord, where pial veins lie next to or within the white matter. The lesions are distributed randomly throughout the brainstem, spinal cord, and cerebellar peduncles without reference to particular systems of fibers, but always confined predominantly to the white matter. In the cerebral cortex and spinal structures, the acute lesions destroy myelin sheaths but leave the nerve cells mostly intact. Severe and more chronic lesions, however, may destroy axons and neurons in the affected region, but the dominant lesion is still demyelinating.