= most frequent form of chronic inflammatory demyelinating disease of unknown etiology, which reduces the lipid content and brain volume; characterized by a relapsing + remitting course

Prevalence: 6÷10,000 (higher frequency in cooler climates; increased incidence with positive family history)

Cause: ? viral / autoimmune mechanism

Peak age: 25–30 (range, 20–50) years; M÷F = 2÷3

Histo:

1. acute stage: perivenular inflammation (at junctions of pial veins) with
   • hypercellularity (= infiltration of lipid-laden macrophages + lymphocytes)
   • well-demarcated demyelination (destruction of oligodendroglia with loss of myelin sheath)
   • reactive astrocytosis (= gliosis), initially with preservation of axons (= denuded axons) → scar (= white matter plaque)
2. chronic stage: plaques advance to fibrillary gliosis with reduction in inflammatory component

Clinical forms:

1. relapsing remitting
2. relapsing progressive
3. chronic progressive

• waxing and waning course with
  • numbness, dysesthesia, burning sensations
  • signs of brain neoplasm: headaches, seizures, dizziness, nausea, weakness, altered mental status, ataxia, diplopia
  • optic neuritis = retrobulbar pain, central loss of vision, afferent pupillary defect (Marcus Gunn pupil)
  • trigeminal neuralgia (1–2%)
• Schumacher criteria:
  1. CNS dysfunction
  2. Involvement of two / more parts of CNS
  3. Predominant white matter involvement
  4. ≥2 episodes lasting >24 hr less than 1 month apart
  5. Slow stepwise progression of signs + symptoms
  6. At onset 10–50 years of age
• Rudick red flags (suggests diagnosis other than MS):
  1. No eye findings
  2. No clinical remission
  3. Totally local disease
  4. No sensory findings
  5. No bladder involvement
  6. No CSF abnormality
• Brain
  Location:
  • subependymal periventricular location (along lateral aspects of atria + occipital horns), corpus callosum, internal capsule, centrum semiovale, corona radiata, optic nerves, chiasm, optic tract, brainstem (ventrolateral aspect of pons at 5^th nerve root entry), cerebellar peduncles (CLASSIC), cerebellum; rather symmetric involvement of cerebral hemispheres; subcortical U fibers NOT spared
    • 10% of MS lesions occur in gray matter!
  • Number + extent of plaques correlate with duration of disease + degree of cognitive impairment
  • lesion size of 1–25 (majority between 5 and 10) mm:
    • large lesions may masquerade as brain tumors
    • mass effect / edema in active lesions (infrequent)
  • ovoid lesions (86%) oriented with their long axis perpendicular to ventricular walls ← perivenous demyelination (pathologically described as “Dawson fingers”)
  • chronic plaques do not enhance ← intact blood-brain barrier
  • diffuse cerebral atrophy (21–45–78%) in chronic MS: enlarged ventricles, prominent sulci
  • lesion enhancement ← breakdown of blood-brain barrier in demyelinating process (irrespective of clinical symptoms):
    • peripheral enhancement of lesion
    • occasionally central enhancement
  
  CT:
  • normal CT scan (18%)
  • periventricular (near atria) multifocal nonconfluent lesions with distinct margins (lesion location does NOT always correlate well with symptoms)
    1. NECT: isodense / lucent
    2. CECT: transient enhancement during acute stage (active demyelination) for about 2 weeks; may require double dose of contrast; ultimately disappearance / permanent scar
  
  MR (modality of choice; 95–99% specific):
  • well-marginated discrete foci of varying size with high signal intensity on T2WI + proton density images (= loss of hydrophobic myelin produces increase in water content); hypointense on T1WI
  • abnormally bright signal of the optic nerve + variable swelling (optic neuritis) with loss of “doughnut” sign of the normal optic nerve complex
  • Gd-DTPA enhancement of lesions on T1WI (up to 8 weeks following acute demyelination with breakdown of blood-brain barrier)
    • characteristically as a solid lesion / incomplete ring
  • lesions on undersurface of corpus callosum (CHARACTERISTIC on sagittal images)
• Spinal cord (in up to 80%)
  • Most common demyelinating process of spinal cord!
  • In 12–33% without coexistent intracranial plaques!
  • number + extent of plaques correlate with degree of disability
  
  Location: predilection for cervical cord
  Site: eccentric involvement of dorsal + lateral elements abutting subarachnoid space
  • atrophic plaques oriented along spinal cord axis
  • length of plaque usually less than 2 vertebral body segments + width less than half of cross section
  • acute tumefactive MS = cord swelling with enhancement
  • cord atrophy in chronic MS
  
  DDx:
  1. Acute transverse myelitis
  2. Cord tumor (follow-up after 6 weeks without decrease in size of lesion)
  3. Trauma
  4. Infarct
  5. Postviral syndromes

Rx: steroids (incite rapid decrease in size of lesions with loss of enhancement)

DDx:

1. Acute disseminated encephalomyelitis (ADEM), subacute sclerosing panencephalitis (lesions of similar age)
2. Lyme encephalopathy (skin rash)
3. Susac syndrome (encephalopathy + branch retinal artery occlusion + hearing loss)
4. Small vessel ischemia (patients >50 years of age, lesions <5 mm, NOT infratentorial)
5. Enlarged type II Virchow-Robin spaces
6. AIDS, CNS vasculitis, migraine, radiation injury, lymphoma, sarcoidosis, tuberculosis, systemic lupus erythematosus, cysticercosis, metastases, multifocal glioma, neurofibromatosis, contusions