This document discusses demyelinating diseases of the central nervous system, focusing on multiple sclerosis. It describes the typical relapsing-remitting clinical course of MS and symptoms like vision changes, weakness, and abnormal sensations. Imaging plays an important role in diagnosis, and treatments include steroids for acute flares and disease-modifying drugs for long-term management of relapsing-remitting MS. The document also covers related conditions like clinically isolated syndrome and radiologically isolated syndrome.

1. Demyelinating Diseases
of the Central Nervous
System
Reference: Lange clinical neurology and neuroanatomy
Nazanin Ayareh

2. MULTIPLE SCLEROSIS

3. Clinical Features
• 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.

4. • 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; and can include a region of paresthesia and/or weakness, diplopia,
vertigo, optic neuritis, transverse myelitis, ataxia, and/or trigeminal neuralgia.

5. • 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.

6. Other classic symptoms and signs o MS include:
• Uthoff’s phenomenon: recurrence or emergence of
neurologic symptoms with heat
• L’hermitte’s sign: electrical sensation down the spine
with forward flexion of the neck
• Internuclear ophthalmoplegia (INO) due to
disruption of the medial longitudinal asciculus (MLF)
• Afferent pupillary defect due to prior optic neuritis.

7. Neuroimaging in Multiple Sclerosis

9. Clinically Isolated Syndrome
• When a patient presents with a first demyelinating event typical of MS (e.g., optic neuritis, transverse
myelitis, or another focal symptom with suggestive imaging correlate), this is called a clinically
isolated syndrome (CIS). If dissemination in space and time can be proven by MRI at the time of a
first attack, then the diagnosis of MS can be made by McDonald Criteria.
• Based on evidence that vitamin D defficiency may be associated with an increased risk of the
development of MS, many practitioners initiate vitamin D supplementation in patients with CIS.
• If patients with CIS do not meet clinical-radiologic criteria for MS, some practitioners elect to look for
ancillary evidence that could support increased risk for subsequent development of MS such as
cerebrospinal fluid (CSF) oligoclonal bands or visual evoked potentials.

10. Radiologically Isolated Syndrome
• Occasionally, an MRI performed for another reason (e.g., headache) may
demonstrate what appears to be a “textbook” appearance of MS, but the
patient has had no clinical attacks and has a normal neurologic examination.
This is called radiologically isolated syndrome (RIS). Such patients are typically
followed clinically and with serial imaging. About one third of patients with RIS
will eventually develop MS and have presumably been discovered in the
preclinical stage, while many appear never to develop any clinical features of the
disease.

11. Treatment
• Acute Treatment of Flares
• Acute attacks of demyelination are typically treated with a 3–5 day course of IV
methyprednisolone.
• Treatment of Progressive Multiple Sclerosis is largely supportive.
• Symptomatic Management in Multiple Sclerosis
• Fatigue: amantadine, modafinil
• Gait: dalfampridine (contraindicated if seizures or renal failure)
• Spasticity: baclofen, tizanidine, botulinum toxin
• Bladder dysfunction: anticholinergics (e.g., oxybutynin), alpha-blockers (e.g., terazosin)
• Depression: psychiatric/psychological care, selective serotonin reuptake inhibitors (SSRIs)

12. Long-term
Treatment
of
Relapsing-Remitting
MS