Multiple sclerosis: Clinical sciences

Multiple sclerosis, or MS for short, is an autoimmune condition characterized by demyelinating CNS lesions that are disseminated in space and time, resulting in neurologic symptoms and deficits. Based on the initial pattern of symptom progression, MS can be classified as relapsing-remitting, which is associated with stable neurologic disability between episodes of attacks; or primary progressive MS, which is characterized by progressive neurologic decline without relapses.

Now, when a patient presents with chief concerns suggesting MS, first obtain a focused history and physical examination, and order a brain and spine MRI with contrast. You can also consider performing a lumbar puncture to analyze the cerebrospinal fluid, or CSF, for oligoclonal bands. If you do, remember to check serum oligoclonal bands for comparison, to see if the bands are only present in the CSF, which confirms intrathecal production of immunoglobulin G.

History will reveal an episode of unexplained neurologic symptoms that develop over hours to days and last for at least 24 hours. Some common symptoms include vision loss, painful eye movements, double vision, slurred speech, facial or limb numbness or weakness, imbalance or incoordination, and vertigo.

Your patient might also report symptoms of trigeminal neuralgia, such as intense, sharp facial pain provoked by touch.

History typically does not reveal fever or other symptoms suggesting infection. Additionally, some patients might notice their symptoms temporarily worsen with heat or during a hot shower, which is known as the Uhthoff phenomenon; while others might report an electric shock sensation down their back when they bend their neck forward, which is known as the Lhermitte sign.

History might also reveal symptoms indicating autonomic dysfunction, like bladder, bowel, or erectile dysfunction; and some patients may describe depression or fatigue.

Although MS can affect anyone, most patients are biological females who present during early adulthood.

Finally, some patients may report risk factors, such as prior Epstein-Barr virus infection, vitamin D deficiency, tobacco use, and living at high latitudes.

As for the exam, findings are variable and depend on the location of the lesions. If your patient has optic nerve inflammation, also known as optic neuritis, the exam may reveal a relative afferent pupillary defect.

You can identify this defect by using the swinging flashlight test to assess the pupillary reflex pathway, which includes the optic nerve as the sensory afferent limb and the oculomotor nerve as the motor efferent limb.

To perform the test, shine a penlight back and forth between both eyes. Normally, the sensory afferent limb of the optic nerve will send a signal to the Edinger-Westphal nucleus in the midbrain.

From here, the signal travels back through the oculomotor nerves and the ciliary ganglia to the pupillary sphincter muscles in both eyes, causing both pupils to constrict.

However, if there’s a lesion within the afferent pathway, when you swing the light from the normal eye to the affected one, the stimulus won’t reach the Edinger-Westphal nucleus. Consequently, efferent signals won’t be sent to the pupillary sphincter muscles, and the pupils will not constrict. Instead, they will dilate, which is known as a relative afferent pupillary defect or Marcus Gunn pupil.

Other possible findings of optic neuritis include decreased visual acuity and red desaturation, meaning red colors appear washed out or lighter in the affected eye.

Now, here’s a clinical pearl to keep in mind! If your patient has optic neuritis, additional testing with visual evoked potentials, which assesses the signal transmission of visual stimuli, or optical coherence tomography, which measures the thickness of retinal layers, will be abnormal.

The eye exam might also reveal internuclear ophthalmoplegia (INO), which results from demyelinating lesions of the medial longitudinal fasciculus in the dorsomedial brainstem.

This part of the brainstem connects cranial nerves III and VI on opposite sides, to coordinate gaze. If your patient has a lesion in this area, during lateral gaze you'll see impaired adduction in one eye and nystagmus of the contralateral abducting eye.

In addition to ocular findings, you might also notice dysarthria, sensory loss or weakness of the face or limbs, as well as spasticity and hyperreflexia. Some patients may demonstrate a Babinski sign, which refers to dorsiflexion and fanning of the toes, indicating upper motor neuron disease. Finally, you might notice limb or gait ataxia.

As for imaging, the MRI will demonstrate both enhancing and non-enhancing hyperintense lesions on the T2 sequence, particularly in the periventricular-, cortical- or juxtacortical-, infratentorial-, and spinal cord regions.

On sagittal imaging, you'll see multiple demyelinating plaques radiating outward from the ventricles, known as Dawson fingers! If the patient has optic neuritis, you might also see edema and enhancement of the optic nerve. Finally, the presence of CSF-specific oligoclonal bands also suggests MS.