Chapter 21: Demyelinating Diseases of the Central Nervous System

INTRODUCTION

This chapter focuses on the following central nervous system demyelinating diseases:

• Multiple sclerosis (MS)

• Neuromyelitis optica (NMO)

• Acute disseminated encephalomyelitis (ADEM)

• Optic neuritis

• Transverse myelitis

Optic neuritis and transverse myelitis may be caused by a primary central nervous system (CNS) demyelinating disease (e.g., MS, NMO), systemic autoimmune disease, or may occur in the setting of infection, following infection, or as paraneoplastic conditions.

Demyelinating diseases of the peripheral nervous system (e.g., acute inflammatory demyelinating polyradiculoneuropathy [AIDP] and chronic inflammatory demyelinating polyradiculoneuropathy [CIDP]) are discussed in Chapter 27.

MULTIPLE SCLEROSIS

Clinical Features of Multiple Sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the CNS that occurs more commonly in young women and is more prevalent further from the equator. In its most common clinical course, patients have multiple flares of symptoms at multiple time points, and recover from these attacks to varying degrees (relapsing-remitting MS). Later in the disease, patients with a relapsing-remitting course may enter a period of progressive decline, a scenario referred to as secondary progressive MS. Primary progressive MS is the least common clinical phenotype of MS, and is typically a spinal cord predominant illness with steady clinical decline from the time of onset rather than relapses and remissions. Even more rarely, the disease may present fulminantly with large tumor-like lesions (Marburg variant, tumefactive demyelination, or Balo’s concentric sclerosis).

Flares of MS present as focal neurologic deficits that emerge and evolve over hours to days and usually resolve completely or near completely in subsequent days to weeks. Deficits are referable to central nervous system sites (brain, brainstem, optic nerve, cerebellum, and/or spinal cord) and can include a region of paresthesias and/or weakness, diplopia (due to disruption of ocular-motor white matter tracts in the brainstem), vertigo (due to demyelination of the cranial nerve 8 entry zone or in the cerebellum), optic neuritis, transverse myelitis, ataxia, and/or trigeminal neuralgia. Trigeminal neuralgia occurs due to demyelination at the trigeminal entry zone in the pons (the nerve itself is peripheral; see “Trigeminal Neuralgia” in Chapter 13). Although MS is not a common cause of trigeminal neuralgia, unilateral or bilateral trigeminal neuralgia in a young patient should lead to consideration of and evaluation for MS.

Between flares of MS, the accumulation of subclinical lesions may cause cognitive symptoms, neuropsychiatric symptoms, and/or fatigue, but progression of focal neurologic deficits between attacks is uncommon in relapsing-remitting MS. On neurologic examination, patients often demonstrate upper motor neuron signs on examination (e.g., hyperreflexia, clonus, Babinski’s sign[s]) even outside of regions of new or prior clinical symptoms due to subclinical lesions that have caused CNS damage without having caused clinical flares.

Other classic symptoms and signs of MS include:

• Uthoff’s phenomenon: recurrence or emergence of neurologic symptoms with ...