Cerebellar Signs

As some of their earliest manifestations, MS patients often develop ataxia, intention tremor, and other signs of cerebellar and cerebellar outflow tract injury. When the cerebellum is involved, patients typically develop an ataxic gait (see Fig. 2-13); however, with minimal involvement, patients’ gait impairment may consist only of difficulty walking in a heel-to-toe (tandem gait) pattern. Cerebellar involvement also typically causes scanning speech, a variety of dysarthria analogous to a “speech ataxia,” characterized by irregular cadence and uneven emphasis on words. For example, when asked to repeat a pair of short syllables, such as “ba…ga…ba…ga…,” a patient might place unequal stress on different syllables, blur them together, or pause excessively. Other manifestations of cerebellar involvement include intention tremor (see Fig. 2-11), dysdiadochokinesia, and an irregular, conspicuous, head tremor (titubation).

Sensory Disturbances

Both lack of sensation and abnormal sensations occur frequently and prominently. Patients often describe hypalgesia, paresthesias, or dysesthesias in their limbs or trunk, or below a particular spinal cord level. They typically lose the ability to appreciate vibration and position sensations more than other sensations. At their onset, sensory symptoms may not conform to commonplace neurologic patterns or be unaccompanied by objective findings. Physicians may understandably mistake this situation as a psychogenic disturbance.

Ocular Impairments

Impaired visual acuity and disordered ocular motility – which neurologists lump together as “eye signs” – occur frequently not only at the onset of MS but also throughout its course. In fact, the absence of eye signs in patients believed to have MS may prompt neurologists to reconsider the diagnosis (see later).

Decreased Visual Acuity

The optic nerve is involved in MS because its covering consists entirely of CNS myelin. The acoustic nerve (cranial nerve VIII) is only partially covered by CNS myelin and is rarely, if ever, involved in MS. No other cranial nerves are covered by CNS myelin.

Neurologists usually attribute visual acuity impairment in MS to inflammation in the retrobulbar portion of the optic nerve, retrobulbar neuritis (optic neuritis) (see Fig. 12-6). Optic neuritis typically causes an irregular area of visual loss in one eye, a scotoma, that often includes the center of vision (Fig. 15-2). It also leads to color desaturation, in which colors, especially red, lose their intensity.

FIGURE 15-2 Optic or retrobulbar neuritis impairs vision in a large, irregular area (scotoma) of the affected eye.

In addition to reducing vision, optic neuritis characteristically causes pain in the affected eye. Probably because ocular movement puts traction on an inflamed optic nerve, eye pain increases when patients look from side to side.

Optic neuritis, as well as other lesions of the optic nerve, causes a readily identifiable, surprising pupillary light reaction (see Fig. 4-2). Swinging a flashlight from the normal eye to the one with optic neuritis will lead to dilation, rather than continued constriction, of both pupils. This paradoxical, unilateral reaction results from less light entering the pupillary reflex arc compared to when the light was shone into the normal eye. Sometimes called the “swinging flashing test,” this abnormality in the afferent limb of the light reflex results in an afferent pupillary defect or “Marcus Gunn” pupil, which neurologists interpret as a sign of optic nerve pathology.

Unless the optic disk is swollen, routine ophthalmoscopic examination usually reveals no abnormality. This discrepancy between visual loss and the normal appearance of the disk has given rise to the saying, “The patient sees nothing and the physician sees nothing.” As an optic neuritis attack subsides, most vision returns and pain subsides. However, with repeated attacks, progressive visual loss ensues and the disk becomes atrophic.

Statistics vary on the relationship of optic neuritis to MS. They indicate that approximately 25% of MS patients present with optic neuritis as their initial symptom and 50% of MS patients suffer an attack during their illness. A single attack of optic neuritis with no other neurologic symptoms and an MRI showing no lesions means that the individual has only about a 25% likelihood of developing MS in the following 10 years; however, when one or more MRI lesions accompany optic neuritis, the individual’s likelihood increases to about 70% during the same period.

Ocular Motility Abnormalities

MS also causes ocular motility abnormalities, including nystagmus and the characteristic internuclear ophthalmoplegia (INO), which is also known as the medial longitudinal fasciculus (MLF) syndrome. Either brainstem or cerebellar involvement can cause nystagmus. Although it is clinically indistinguishable from nystagmus induced by other conditions (see Chapter 12), MS-induced nystagmus typically occurs in combination with dysarthria and tremor (Charcot’s triad).

In MS-induced INO, MLF demyelination interrupts nerve impulse transmission from the pontine conjugate gaze centers to the oculomotor nuclei (Figs 15-3 and 15-4). The primary symptom of INO is diplopia on lateral gaze because of paresis of the adducting eye. INO is strong evidence of MS; however, systemic lupus erythematosus (SLE or lupus [see later]) and small basilar artery strokes may also cause it. In addition, Wernicke–Korsakoff syndrome, myasthenia gravis, and botulism can produce patterns of ocular muscle weakness that mimic INO. From a physiologic viewpoint, INO is analogous to a disconnection syndrome, such as conduction aphasia, in which communicating links are severed but each neurologic center remains intact (see Chapter 8).

FIGURE 15-3 Under normal conditions, when looking laterally, the pontine conjugate gaze center stimulates the adjacent abducens (sixth) nerve nucleus and, through the medial longitudinal fasciculus (MLF), the contralateral oculomotor (third) nerve nucleus. For example, when looking to the right, as in this illustration, the right pontine gaze center stimulates the right abducens and the left oculomotor nuclei (see Fig. 12-12).

FIGURE 15-4 In internuclear ophthalmoplegia (INO), also known as the MLF syndrome, an interruption of the medial longitudinal fasciculus (MLF) prevents impulses from reaching the oculomotor (third) nuclei. Because those nuclei themselves remain intact, the pupils and eyelids are normal in both eyes. However, when looking to the right, because the left oculomotor nucleus is not stimulated, the left eye fails to adduct. The right eye abducts, but nystagmus develops. With bilateral INO, which is characteristic of multiple sclerosis (MS), neither eye adducts and abducting eyes have nystagmus.

Spinal Cord Symptoms and Signs

Patients with spinal cord involvement, typically the primary and sometimes the only source of disability in primary progressive MS, have paraparesis with hyperactive deep tendon reflexes and Babinski signs. They usually have three troublesome, common symptoms (the three Is) – incontinence, impotence, and impairment of gait. Another troublesome, often incapacitating feature of spinal cord involvement consists of spasticity of the legs. Even in the absence of paraparesis, spasticity impairs patients’ gait and causes painful leg spasms. Patients with cervical spinal cord involvement often describe electrical sensations, elicited by neck flexion, that extend from the neck down the spine (Lhermitte’s sign).

Spinal cord involvement also typically leads to urinary incontinence from a combination of spasticity, paresis, and incoordination (dyssynergia) of the bladder sphincter muscles (Fig. 15-5). MS patients initially often have incontinence during sleep and sexual intercourse. As the disease progresses, patients develop intermittent urinary retention and then complete loss of control. They often require intermittent or continuous catheterization, which leads to frequent, chronic, or recurrent urinary tract infections.

FIGURE 15-5 The urinary outflow of the bladder has two sphincters: an internal sphincter controlled by the autonomic nervous system (ANS), and an external one under voluntary control. Normal urinary bladder emptying (urination) occurs when the detrusor (wall) muscle contracts and both sphincter muscles relax. Purposefully urinating requires voluntary action (to relax the external sphincter) and reflex parasympathetic (ANS) activity (to contract the detrusor and relax the internal sphincter). Urinary retention occurs with either anticholinergic medication or excessive sympathetic activity because both inhibit detrusor contraction and internal sphincter muscle relaxation. Urinary retention also occurs with spinal cord injury because the external sphincter is unable to relax because it is spastic and paretic (dyssynergic).

Erectile dysfunction, decreased desire, and other forms of sexual impairment plague the majority of MS patients (see Chapter 16). About 40% of women with MS do not engage in sexual intercourse. Even before developing erectile dysfunction, men often experience premature or retrograde ejaculation. Sexual dysfunction, with or without urinary incontinence, is attributable to MS involving the spinal cord. With spinal cord damage severe enough to cause paraplegia, men have lowered and abnormal sperm production, but women can conceive and bear children.

Fatigue and Other Important Symptoms

An inexplicable generalized, daily sense of fatigue, which neurologists sometimes call “lassitude” (weariness of body or mind), affects about 50–80% of MS patients. This symptom, which is entirely subjective, does not correlate with patients’ age or degree of paresis. It reduces MS patients’ compliance with medical regimens, quality of life, ability to work, and compliance with medical regimens. In addition, it intensifies other MS symptoms, including depression and cognitive impairment.

MS-induced fatigue represents a physiologic cause of the chronic fatigue syndrome (see Chapter 6). Although many, but not all, studies found that depression is comorbid, antidepressants do not alleviate MS-induced fatigue.

Various pain syndromes also commonly occur in MS. For example, approximately 2% of MS patients suffer from trigeminal neuralgia (see Chapter 9) and 10% Lhermitte’s sign. Many MS patients have pain in their limbs or trunk. These pains probably arise from MS plaques irritating CNS pain-transmitting fibers in, respectively, the brainstem and cervical spinal cord. As with other forms of neuropathic pain (see Chapter 14), antiepileptic drugs, such as gabapentin and carbamazepine, provide some relief.

Because MS, in general, spares CNS structures that contain little or no myelin, symptoms that originate in gray-matter injury rarely complicate the illness. For example, MS patients seldom develop signs of focal cerebral cortical dysfunction, such as seizures or aphasia. Similarly, because the basal ganglia, like the cerebral cortex, are devoid of myelin, MS patients almost never develop involuntary movement disorders (see Chapter 18).