Patients with MS are evaluated by clinical examination, laboratory testing, neuroimaging, and neurophysiological studies. The clinical manifestations of MS and the lesions that cause them vary over the course of the disease (dissemination in time and space). Diagnostic classification is problematic (p. 216) if only one lesion is found (e.g., by MRI), if symptoms and signs are in only one area of the CNS (e.g., spinal cord), or if only one attack has occurred (Table 27, p 375).
■ Clinical Manifestations
Sensory deficits, upper-motor-neuron paresis, incoordination, visual impairment (field defects), nystagmus, internuclear ophthalmople-gia, and/or bladder dysfunction are common signs of MS. Complaints of pain, paresthesiae, abnormal fatigability, or episodic disturbances are often, by their nature, difficult to objectify. Clinical examination may reveal no abnormality because of the episodic nature of the disease itself.
■ Laboratory Tests and Special Studies
Evoked potentials. Visual evoked potential (VEP)
studies reliably detect optic nerve lesions, but neuroimaging is better for detecting lesions of the optic tract or optic radiation. VEP reveals prolongation of the P100 latency in one eye and/ or an abnormally large discrepancy between the latencies in the two eyes in roughly 40% of MS patients without known optic neuritis, and in almost half of those with early optic neuritis. Somatosensory evoked potential (SEP) studies of the median or tibial nerve typically reveal prolonged latencies in MS. Low amplitude of evoked potentials, on the other hand, often indicates a pathological process of another type, e. g. tumor. SEP abnormalities are found in up to 60% of MS patients with predominantly sensory manifestations. Auditory evoked potential (AEP) studies are less sensitive in MS than VEP or SEP. The most common AEP change is prolongation of latency. AEP studies are helpful for the further classification of vertigo, tinnitus, and hearing loss. Motor evoked potential (MEP) studies reveal prolonged central conduction times when CNS lesions involve the pyramidal pathway. The sensitivity of MEP in MS is approximately the same as that of SEP. MEP studies can provide supporting evidence for MS in patients with latent paresis, gait disturbances, abnormal reflexes, or movement disorders that are difficult to classify.
Tests of bladder function. The residual urine volume can be measured by ultrasound. It should not exceed 100 ml in patients with a normal bladder capacity of 400-450 ml; in general, it should normally be 15-20% of the cys-tomanometrically determined bladder volume. Urodynamic electromyography (EMG) provides more specific data concerning bladder dysfunction.
Neuroimaging. CT may reveal other diseases that enter into the differential diagnosis of MS (e. g., brain tumor) but is insufficiently sensitive (ca. 25-50%) to be useful in diagnosing MS itself. MRI scans reveal the characteristic foci of demyelination disseminated in the CNS (MS plaques); contrast enhancement is seen in acute but not in chronic lesions. The sensitivity of MRI for MS is greater than 90%, but its specificity is considerably lower; thus, the MRI findings alone cannot establish the diagnosis. CSF examination. CSF abnormalities are found in more than 95% of MS patients. The cell count rarely exceeds 20 cells/mm3. The total protein concentration is elevated in ca. 40% of patients, and intrathecal IgG synthesis (IgG index) in ca. 90%. Oligoclonal IgG is found in 95% of MS patients, and antibodies to mumps, measles and herpes zoster in 80%.
The early course of MS varies among patients in accordance with the variable extent of the inflammatory lesions and disturbances of the blood-brain-barrier. The severity of late manifestations is correlated with the number of plaques. It is hypothesized that MS is caused by a combination of genetic (polygenic) predisposition and exogenous factors (viral or bacterial infection?) that induces an inappropriate immune response to one or more CNS autoantigens (see p. 220) that have not yet been identified.
MRI (T2-weighted image of cerebral hemispheres)
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