Demyelinating and Inflammatory Disorders of the Central Nervous System

Symptomatic Onset

The initial focal manifestations may be acute or insidious and can vary in severity. Acute neurologic deficits caused by MS are called relapses and are known as flares, attacks, or exacerbations. The most common initial symptoms are sensory disturbances, visual loss, and weakness, although abnormal gait, loss of dexterity, diplopia, ataxia, vertigo, or sphincter disturbances can occur. Nonspecific symptoms such as malaise or fatigue often precede the initial focal disturbance.

Sensory Disturbance

The most common presenting symptom of MS is paresthesia (tingling, pins and needles), dysesthesia (burning, gritty, sandy, electrical, or wet sensations), or hypesthesia (loss of sensation or procaine-like numbness). Some patients describe a squeezing sensation as if a limb or the trunk were tightly wrapped. These symptoms can be intermittent or constant and can spread from one location to adjoining areas. Spinal cord involvement is implied by ascending numbness with a sensory level. A Lhermitte symptom, an electrical or shocklike paresthesia that radiates down the spine and into one or more limbs after neck flexion, localizes the lesion to the cervical spine. Sensory disturbances associated with MS flares usually resolve spontaneously but sometimes evolve into chronic neuropathic pain. Trigeminal neuralgia also occurs in MS, perhaps caused by demyelination in the root entry zone of the trigeminal nerve.

Optic Neuritis

The next most common presenting manifestation of MS is optic neuritis, which causes loss of vision affecting usually one eye evolving over hours or days. Bilateral simultaneous optic neuritis is much less frequent and should raise the possibility of an alternate diagnosis such as neuromyelitis optica spectrum disorder (NMOSD). Loss of vision can be complete or partial; patients will often report a scotoma, which is an area of diminished or blurred vision in the monocular field. Optic neuritis is often associated with periorbital pain elicited by eye movements. Loss of vision can be subtle and affect only color vision. Red desaturation, or the inability to distinguish shades of red, can be quantified using Ishihara color plates. Demyelination of the optic nerve close to the retina causes optic disc pallor. The differential diagnosis of acute visual loss is shown in Table 21.1 .

Motor Symptoms

Motor symptoms are as common as optic neuritis as initial manifestations of MS and include limb weakness, loss of dexterity, and gait disturbance. Symptoms typically evolve over hours or days; sometimes patients will awaken with a motor deficit. Weakness can affect a single limb or cause hemiparesis or paraparesis. The hemiparesis of MS usually spares the face. Sometimes weakness becomes apparent only during exertion. Weakness is usually accompanied by spasticity and hyperreflexia.

Diplopia

Dysconjugate eye movements resulting in diplopia are common in MS. Intranuclear ophthalmoplegia (INO) is caused by demyelinating plaques within the medial longitudinal fasciculus (MLF). Lesions in the MLF typically occur ipsilateral to the affected third nucleus and result in impaired ipsilateral adduction with compensatory nystagmus of the abducting eye. MS also can cause vertical diplopia and isolated impairments of the sixth, third, and fourth nerves.

Ataxia and Tremor

Dyscoordinated movements of the limbs or trunk are common in MS because of plaques affecting the cerebellar afferent or efferent pathways and range in severity from subtle to disabling. Tremor and dysmetria, an error in measurement of movement, are often observed on finger-nose-finger and heel-knee-shin tests. Dysrhythmia can be demonstrated by finger or toe tapping. Romberg sign, truncal swaying on standing with the feet together and eyes closed, can be caused by impaired proprioception from spinal cord dorsal column lesions.

Neuropsychiatric Dysfunction

Cognitive impairments are present in 40% to 65% of MS patients and can result in loss of vocation and impairment of activities of daily living. Patients often report difficulties with short-term memory, attention, information processing, problem-solving, multitasking, and language function. Cognitive deficits may not be detected by the Mini-Mental Status Examination and often require neuropsychiatric testing. Emotional lability is common; up to 60% of MS patients suffer from depression.

Bladder and Bowel Dysfunction

Patients often complain of urinary urgency, frequency, hesitancy, and incontinence. Incontinence can occur in the setting of a spastic bladder that is incapable of filling completely or with a distended (denervated) bladder that overflows. It is often not possible to determine the nature of bladder dysfunction by history. Measurement of the volume of postvoid residual urine, by catheterization, ultrasound, or urodynamic studies, is essential for distinguishing between a spastic and denervated bladder. Bladder dyssynergia, an impairment of sphincter and detrusor coordination, also is a cause of hesitancy and incomplete voiding. Patients with urinary retention are susceptible to urinary tract infections, and such infections may trigger MS relapses by stimulating the immune system.

Bowel dysfunction is common in MS and is presumably caused by spinal cord plaques. Chronic constipation can worsen spasticity. Incontinence occurs either as a consequence of sphincter dysfunction or from bowel spasticity and fecal urgency.

Vertigo

Vertigo caused by MS is sometimes associated with other signs or symptoms of brain stem pathology such as facial sensory loss or diplopia. Vertigo can be fleeting or last for days or even weeks. Although uncommon, unilateral hearing loss occurs in MS, sometimes in conjunction with vertigo. Vertigo caused by labyrinthine pathology identified by the Dix-Hallpike maneuver (see Chapter 14 ) is not caused by MS.

Dysarthria

Impairments of speech are common in MS and can be caused by tongue weakness from lower brain stem dysfunction, spastic dysarthria from corticobulbar injury, or scanning dysarthria from cerebellar dysfunction.

Dysphagia

Impairment of swallowing occurs in MS, particularly later in the course of the disease. Choking on thin liquids is consistent with neurologic injury as opposed to solid food dysphagia, which is typically caused by a pharyngeal structural abnormality. Barium swallow and fiberscope endoscopic evaluation of swallowing are helpful in assessing aspiration risk.

Facial Weakness

Lower motor neuron facial weakness, similar to Bell palsy, can occur when MS plaques affect intraparenchymal emerging fibers of the seventh cranial nerve. Ipsilateral loss of taste, hyperacusis, retroauricular pain, and synkinesis are hallmarks of peripheral facial neuropathy and do not occur with central facial weakness. Facial myokymia is a chronic flickering contraction of the orbicularis oculi or other muscles of facial expression caused by injury to the facial nerve or corticobulbar tracts within the brain stem.

Fatigue

Fatigue is the most common symptom of MS and contends with cognitive impairment as the major cause of loss of vocation. Fatigue can occur as a consequence of exertion (neuromuscular weakness), as a manifestation of depression, as a consequence of insomnia (daytime drowsiness), or as a generalized lassitude. Fatigue is often worse in the afternoon but can be present on awakening and persist throughout the day.

Paroxysmal Symptoms

Virtually all symptoms of MS, including the Lhermitte symptom, sensory disturbances, weakness, ataxia, vertigo, and diplopia, can occur as transient paroxysms lasting for seconds to minutes, sometimes in clusters. Flexor spasms are brief tonic spasms of a limb or the face and often occur at night and in clusters. Flexor spasms are frequently preceded by paresthesias and can be elicited by movements, hyperventilation, or other precipitating factors.