Sagittal FLAIR images - Stable nonenhancing hyperintensities within the pericallosal white matter and bilateral centrum semiovale, consistent with known history of multiple sclerosis

Sagittal FLARE MRI - Stable nonenhancing hyperintensities within the pericallosal white matter and bilateral centrum semiovale, consistent with known history of multiple sclerosis

Axial T2, axial FLARE

Jaimie Lynn Maines, MS-IV SYB #3 5 March 2008 Multiple Sclerosis Jaimie Lynn Maines, MS-IV SYB #3 5 March 2008

What is Multiple Sclerosis? Chronic, inflammatory, demyelinating disease that affects the CNS Onset usually in young adulthood Women > men Affects neurons in white matter of brain and spinal cord Destroys oligodendrocytes  loss of myelin sheath MS is the most common autoimmune inflammatory demyelinating disease of the central nervous system. Neurons in the white matter carry signals in between the gray matter areas, where the processing is done, and between these and the rest of the body. oligodendrocytes - cells responsible for creating and maintaining a fatty layer, know as the myelin sheath, which helps the neurons carry electrical signals MS results in thinning or complete loss of myelin and, less frequently, the cutting (transection) of the neuron’s extensions or axons. When the myelin is lost, the neurons can no longer effectively conduct their electrical signals. The name MS refers to the scars (scleroses - better known as plaques or lesions) in the white matter. Loss of myelin in these lesions causes some of the symptoms of MS. Theory behind cause of disease - results from attacks to the nervous system by the body’s own immune system.

Signs and Symptoms Changes in sensation (hypoesthesia) Muscle weakness Abnormal muscle spasms Difficulty with movement Ataxia Dysarthria Dysphagia Nystagmus, optic neuritis, diplopia Fatigue and acute or chronic pain syndromes Bladder and bowel difficulties Cognitive impairment, depression Lhermitte’s Sign Classic finding in MS Loss of myelin in plaque lesions of white matter causes some of the symptoms seen in MS. Symptoms vary widely depending upon which signals are interrupted. More advanced forms of imaging are now showing that much of the damage happens outside the plaque regions. Almost any neurological symptom can accompany the disease. Lhermitte’s Sign, sometimes called the Barber Chair phenomenon, is an electrical sensation that runs down the back and into the limbs, and is produced by bending the neck forward. The sign suggests a lesion of the dorsal columns of the cervical cord or of the caudal medulla.

Disease Course and Clinical Subtypes Relapsing Form - new symptoms occur in discrete attacks Progressive Form - new symptoms slowly accumulate over time Relapse-Remitting Form - between attacks, symptoms resolve completely, but permanent neurological problems persist May develop Secondary Progressive MS Relapsing-remitting: Relapsing-remitting describes the initial course of 85% to 90% of individuals with MS. This subtype is characterized by unpredictable attacks followed by periods of months to years of relative quiet with no new signs of disease activity. Deficits suffered during the attacks may either resolve or may be permanent. When deficits always resolve between attacks, this is referred to as ”benign" MS. Secondary progressive: Secondary progressive describes around 80% of those with initial relapsing-remitting MS, who then begin to have neurologic decline between their acute attacks without any definite periods of remission. This decline may include new neurologic symptoms, worsening cognitive function, or other deficits. Secondary progressive is the most common type of MS and causes the greatest amount of disability. Primary progressive: Primary progressive describes the approximately 10% of individuals who never have remission after their initial MS symptoms. Decline occurs continuously without clear attacks. The primary progressive subtype tends to affect people who are older at disease onset. Progressive relapsing: Progressive relapsing describes those individuals who, from the onset of their MS, have a steady neurologic decline but also suffer superimposed attacks; and is the least common of all subtypes

Diagnosis Difficult to diagnose in early stages Definitive diagnosis cannot be made until other possible causes for symptoms have been ruled out In Relapsing-Remitting: there must be evidence of at least 2 anatomically separate demyelinating events separated by at least 30 days In Primary Progressive: there must be slow progression of si/sx over at least 6 months

McDonald Criteria Clinical data alone - 2 separate episodes of neurologic symptoms characteristic of MS, consistent PE MRI - areas of demyelination appear as bright spots (active plaques enhance with Gad) CSF - evidence of chronic inflammation Oligoclonal bands combined with MRI and PE can make definitive diagnosis Visual or Somatosensory Evoked Potentials - brain with MS responds less actively to stimulation McDonald Criteria represents international efforts to standardize the diagnosis of MS using clinical, laboratory, and radiologic data. MRI - Gad can be used to highlight active plaques; by elimination it can also demonstrate the existence of historical lesions not associated with clinical symptoms. This can provide the evidence of chronic disease needed for a definitive diagnosis of MS. Visual and Somatosensory Evoked Potentials - the brain of a person with MS responds less actively to stimulation of the optic nerve and sensory nerves. Decreased activity on either test can reveal demyelination which may be otherwise asymptomatic.

Imaging Studies MRI Test of choice to support clinical diagnosis Charactertistic lesion - cerebral or spinal plaque; periventricular region, corpus callosum, centrum semiovale, deep white matter structures, basal ganglia Typically ovoid in appearance, arranged at right angles to corpus callosum Hyperintense on T2 MRI, hypointense on T1 Diffusion imaging may identify plaques better Gad-enhancing plaques  active lesions Discrete region of demyelination

T1 weighted MRI, post-contrast of same brain slice performed at monthly intervals. Bright spots indicate active plaques.

Differential Diagnosis Neuromyelitis Optica Autoimmune disease - attack of optic nerves and spinal cord Stroke Acute Disseminated Encephalomyelitis Immune mediated disease of brain following viral infection or vaccination; multiple inflammatory cell deposits found in white matter Lyme Disease Tumors Lupus

Medical Treatment There is NO cure Treatments aimed at returning function following an attack, preventing new attacks, and preventing disability IV steroids for acute attacks Interferon - disease modifying treatment Neurorehabilitation to ease burden of progressive impairment