CNS I Path - Demyelinating Diseases

Question 1

Myelin Review

Answer 1

Specialized cell membrane that wraps around axons - fast conduction

OLIGODENDROCYTES – make CNS myelin and ONE can insulate MANY axons

SCHWANN CELLS - make PNS myelin, and ONE insulates ONE axon

Question 2

DYSmyelinating vs. DEmyelinating

Answer 2

DYSmyelinating – Those that involve the failure of myelin production or the production of ABNORMAL myelin –> progressively FATAL

DEmyelinating –> those that involve the DESTRUCTION and REMOVAL of structurally and biochemically NORMAL myelin (virally induced, bacterially induced, immunologically induced, MS)

Question 3

Virally Induced Demyelinating Diseases

Answer 3

SUBACUTE SCLEROSIS PANENCEPHALITIS –> infection of BOTH oligodendrocytes AND neurons by MEASLES VIRUS!!!

Histology –> Lymphocytes in the neuropil around the blood vessels, watery-flat appearance in the nucleoplasm that is distinguishing from the chromatin of non-infected cells; RARE in the US (immunized!)

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY –> most common in immunocompromised; JC VIRUS; Viral inclusions in the nucleus of the OLIGODENDROGLIAL cells prevent it from myelinating axons; JC usually isn’t a problem in healthy people; deadly

Question 4

Immunologically Induced Demyelinating Diseases

Answer 4

Usually come in a single episode SEVERAL WEEKS AFTER A VIRAL INFECTION

Acute Disseminated Encephalomyelitis –> Creates MULTIPLE ENHANCING LESIONS in the brain that present like a tumor and like a stroke; can affect all ages, difficult diagnosis

Others: Post Infectious encephalomyelitis, acute hemorrhagic leukoencephalitis, GBS

Question 5

Multiple Sclerosis Definition

Answer 5

Chronic disease that manifests as RECURRENT ATTACKS of neurological dysfunction caused by MULTIPLE AREAS OF INFLAMMATION and MYELIN LOSS in both the brain and SC

Variable and very unpredictable!!! Makes initial diagnosis tough

Question 6

Symptoms of MS

Answer 6

Motor –> Weakness, spasticity

Cerebellar –> Gait ataxia, tremor

Sensory –> numbness, parasthesis (tingling, burning), pain

Cognitive –> memory, learning, attention, information processing

Other –> fatigue, vision problems, bladder/bowel dysfunction

Question 7

Clinical Course of MS?

Answer 7

Benign/Mild – 10% of patients; long gaps of normal function with recurrence years later

Relapsing/Remitting – 60% of patients –> rapid episodes with fewer years between attacks

Secondary Progressive – Begin with the relapsing/remitting phase, but then never turn to baseline after years – still have better/worse periods but are ALWAYS progressing

Primary Progressive – these patients get rapidly worse, never return to baseline

Question 8

Pathological Definition of MS

Answer 8

Chronic inflammatory disease of the CNS causing DEMYELINATION, DEATH OF OLIGODENDROGLIAL CELLS, and VARIABLE DEGREES OF TISSUE DAMAGE, INCLUDING AXONAL DAMAGE

Question 9

Gross examination of brain with MS

Answer 9

Dark coloration around ventricles revealing a loss of white matter –> plaques, variable

Question 10

Histology of MS

Answer 10

Sharp border between the ACTIVE MS PLAQUE and the NORMAL MYELIN with lymphocytes and macrophages at the interface –> if the plaques are surrounding veins, they create a demyelinating area called DAWSONS FINGER (lymphocytes are released from veins and just don’t go very far, damage area around vein)

B cells, T cells, complement, microglia, axonal damage, oligodendroglial cell death, antibodies, myelin protein synthesis, endothelial damage (can damage BBB)

Question 11

3 processes cause the clinical symptoms of MS

Answer 11

Inflammation!

Demyelination!

Axonal Loss!!! Progressive and permanent –> acute MS plaques have the most inflammatory cells and most loss; chronic active plaques on the edge of and in the center of the brain experience loss; possible that the axonal loss causes the permanent deficits seen in MS

Question 12

Pathology and predictive value

Answer 12

Pathology DOES NOT CORRELATE with the clinical picture, and thus has NO PREDICTIVE VALUE, so biopsying plaques has no real purpose…MRI is the best bet

Question 13

Random MS epidemiology

Answer 13

Environmental causes clear –> more prevalent FURTHER from the EQUATOR –> younger than 15, move away, increases risk! Older it won’t matter

Move towards equator BEFORE 15, less risk!

Question 14

Genetics and MS

Answer 14

MZ twins – 30% concordance
DZ twins – 5%
2 parents with MS – 9% chance child gets it

Question 15

Overal causative agents?

Answer 15

INFECTIOUS AGENT (autoimmune component) + PREDISPOSITION (Genetics) + ENVIRONMENT = abnormal response

Question 16

Vitamin D and MS

Answer 16

MS patients have LOW LEVELS of Vit D and show bone demineralization early

Correlation with the fact that people at high latitudes have less sun exposure!

Rising concern that people spend less time outdoors –> less sun –> less vit D –> higher risk of MS

Vit D also inhibits CD4 T cell proliferation, so without it, our immune system is already overactive

MS patients are given vitamin D!!!!!