Color Atlas of Neurology

D1 receptor

Occupational therapy

Speech therapy

Physical therapy

Central Nervous System

213

Multiple Sclerosis

214the disease. Spasticity makes its first appearance in the form of extensor spasms; flexor

spasms develop later. The latter are often pain-

ful, cause frequent falls, and, if severe and persistent, can cause flexion contractures (paraplegia in flexion). Many patients complain of abnormal fatigability.

Sensory manifestations. Episodic or continuous paresthesiae (sensations of tingling or numbness, tightness of the skin, heat, cold, burning, prickling) are common, particularly in the early stage of the disease, with or without other manifestations of neurological dysfunction. As the disease progresses, such positive phenomena usually recede and are replaced by sensory deficits affecting all sensory modalities. A constant or only slowly rising sensory level (“sensory transverse cord syndrome”) is uncharacteristic of MS and should prompt the search for a spinal cord lesion of another kind. Many MS patients have Lhermitte’s sign (which is actually a symptom), an electric or coldlike paresthesia traveling from the nuchal region down the spine, sometimes as far as the legs, on flexion of the neck (p. 49). If no other symptoms or signs are present, other causes should be considered (e. g., a cervical spinal cord tumor).

Pain in MS most often appears in the form of trigeminal neuralgia (p. 186), severe pain in the limbs (p. 108), tonic spasms (p. 204), or backaches, sometimes with radiation in a radicular pattern. Other painful phenomena include flexor spasms due to spasticity, contractures, and dysuria due to urinary tract infection.

Visual impairment in MS is usually due to optic neuritis (mostly unilateral), which also produces pain in or around the eye. The impairment begins as blurred or clouded vision and progresses to cause reading impairment and visual field defects (central scotoma or diffuse defects). Marcus Gunn pupils (p. 92) may be observed. Physical exercise, high ambient temperature, menstruation, or cigarette smoking can aggravate existing visual problems (Uhthoff’s phenomenon). Optic neuritis, as an isolated finding, is not necessarily the first manifestation of MS; patients with bilateral optic neuritis have a much lower risk of developing MS than those with the unilateral form. Diplopia is usually due to internuclear ophthalmoplegia (p. 86). Nystagmus (p. 88).

Incoordination. Intention tremor, dysarthria, truncal ataxia, and oculomotor dysfunction are common. Gait unsteadiness due to motor incoordination is often experienced by the patient as dizziness or lightheadedness. Acute vertigo with nausea, vomiting, and nystagmus can also occur.

Inflammatory diseases. Neurosarcoidosis, neuroborreliosis, neurosyphilis, Whipple disease, postinfectious acute disseminated encephalomyelitis (ADEM), progressive multifocal

216leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), HIV infection,

HTLV-1 infection.

Neurovascular disorders. Arteriovenous fistula of spinal dura mater, cavernoma, CADASIL (p. 172).

Hereditary/metabolic disorders. Spinocerebellar ataxias, adrenoleukodystrophy, endocrine diseases, mitochondrial encephalomyelopathy, vitamin B12 deficiency (funicular myelosis).

Tumors of the brain or spinal cord (e. g., lymphoma, glioma, meningioma).

Skull base anomalies. Arnold–Chiari malformation, platybasia.

Myelopathy. Cervical myelopathy (spinal stenosis).

Somatoform disturbances in the context of mental illness.

Prognosis

Favorable prognostic indicators in MS include onset before age 40, monosymptomatic onset, absence of cerebellar involvement at onset, rapid resolution of the initial symptom(s), a re- lapsing-remitting course, short duration of relapses, and long-term preservation of the ability to walk. A relatively favorable course is also predicted if, after the first 5 years of illness, the MRI reveals no more than a few, small lesions without rapid radiological progression and the clinical manifestations of cerebellar disease and central paresis are no more than mild. A benign course, defined as a low frequency of recurrences and only mild disability in the first 15 years of illness, is seen in 20–30% of patients. The disease takes a malignant course, with major disability within 5 years, in fewer than 5% of patients. Half of all MS patients have a second relapse within 2 years of disease onset.

Multiple Sclerosis

Autonomic dysfunction

(urinary/fecal incontinence, sexual dysfunction)

Impaired coordination

Paroxysmal symptoms

(trigeminal neuralgia) Behavioral changes

Central Nervous System

217

Multiple Sclerosis

Diagnosis

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 cystomanometrically 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%.

Pathogenesis

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.

Multiple Sclerosis

Serum

CSF

Lesions

Special tests in MS (IEF = isoelectric focusing)

Central Nervous System

219

Central Nervous System

Multiple Sclerosis

Cerebral lesion (plaque)

Central Nervous System

221

CNS Infections

Syndromes

seizures, generalized weakness, and impairment of consciousness ranging to coma. Immunodeficient patients commonly have fever, headache, stiff neck, and drowsiness in addition to the manifestations of their primary illness.

Meningitic syndrome is characterized by fever, severe, intractable headache and backache, pho-

222tophobia and phonophobia, nausea, vomiting, impairment of consciousness, stiff neck, and hy-

perextended posture, with opisthotonus or neck

pain on flexion. Kernig’s sign (resistance to passive raising of leg with extended knee) and Brudzinski’s sign (involuntary leg flexion on passive flexion of the neck) are signs of meningeal involvement. Painful neck stiffness is due to (lepto)meningeal irritation by infectious meningitis, septicemia, subarachnoid hemorrhage, neoplastic meningitis, or other causes. Isolated neck stiffness not caused by meningitis (meningism) may be due to cervical disorders such as arthrosis, fracture, intervertebral disk herniation, tumor, or extrapyramidal rigidity. Papilledema is usually absent; when present, it indicates intracranial hypertension (p. 158).

Encephalitic syndrome is characterized by headache and fever, sometimes accompanied by epileptic seizures (often focal), focal signs (cranial nerves deficits, especially of CN III, IV, VI, and VII; aphasia, hemiparesis, hemianopsia, ataxia, choreoathetosis), behavioral changes, and impairment of consciousness (restlessness, irritability, confusion, lethargy, drowsiness, coma). The neurological signs may be preceded by limb pain (myalgia, arthralgia), a slight increase in body temperature, and malaise. For acute cerebellitis ( ataxia), see p. 276. Brain stem encephalitis produces ophthalmoplegia, facial paresis, dysarthria, dysphagia, ataxia, and hearing loss.

Myelitic syndrome. Myelitis presents with severe local pain, paraparesis, paresthesiae, or some combination of these. Incomplete or complete paraplegia or quadriplegia (p. 48) develops within a few hours (acute) or days (subacute). The differential diagnosis may be difficult.