Path - Demyelinating

Question 1

What is a leukodystrophy disease?

Answer 1

Inherited disturbances in the formation and preservation of myelin

Question 2

What are three leukodystrophies?

What are the inheritance patterns?

Answer 2

Metachromatic leukodystrophy, Krabbe disease (Globoid cell Leukodystrophy, GCLD), and Adrenoleukodystrophy (ALD)
MLD and GCLD are autosomal recessive. ALD is x-linked recessive

Question 3

What accumulates in metachromatic leukodystrophy?

Answer 3

Cerebroside sufates sulfatides (lipids that contain sulfate

Question 4

Describe Pathology of Metachromatic Leukodystrophy

Answer 4

Accumulation of sulphatides (from a defective arylsufatase-A) cause demyelination and gliosis.
Macrophages containing sulfatides

Question 5

How is Metachromatic Leukodystrophy diagnosed?

Answer 5

Macrophages containing sulfatides bind dyes and become metachromasia. Detecting metachromatic in urine is good diagnostic

Question 6

What is Krabbe disease?

Answer 6

A deficiency in Galactocerbroside B-galatosidase enzyme. The alternative pathway for the breakdown of galactocerebroside creates toxic galactosylsphigosine. The accumulation causes oligodendrocyte and schwann cell injury

Question 7

Krabbe disease is also called what?

Answer 7

Globoid Cell Leukodystrophy

Question 8

What accumulates in Krabbe? Where?

Answer 8

Also called Globoid cell leukodystrophy because of the accumulation of Globoid cells which are multinucleated macrophages. Around the blood vessels

Question 9

Describe ALD.

Answer 9

Adrenoleukodystrophy
X-linked disorder of the Adrenal cortex
with demyelination of the nervous system

Increase in levels of very long chain FA in children and body fluids because of enzyme mutation that degrades VLCFA’s

Increases blood pressure

Also occurs in children 4-8 yrs old

Question 10

Who get leukodystrophies?

Answer 10

Children
MLD = infants; lethal within several years
GCLD = ~ 2 years leathal
ALD = 4-8 yrs

Question 11

Where does Adrenoleukodystrophy degeneration occur?

Answer 11

Cortical white matter of the parietal and occipital regions

Question 12

What laboratory signs will be in ADL?

Answer 12

Serum levels of increase VLCFA’s

Atrophied adrenal glands will also have high levels of VLCFA’s

Question 13

Describe Alexander disease.

Answer 13

Also called Rosenthal Fiber Encephalopathy or fibrinoid leukodystrophy.

Occurs in a mutation of the GFAP (Glial Fibrillay Acidic protein) that causes the formation of Rosenthal fibers.

The extracellular accumulation of Rosenthal fibers cause the degeneration of myelin in the brain`

Question 14

Who gets Alexander disease? Prognosis?

Answer 14

Children and infants mostly get Rosenthal fiber encephalopathy that cause phsychomotor retardation, progressive dementia, paralysis and death

Question 15

What is Multiple Sclerosis

Answer 15

An autoimmune demyelinating disease that attacks the CNS but spares the PNS

Question 16

Who gets Multiple sclerosis?

Answer 16

Young adults in 30-40s

People in colder climates

Question 17

What Pathology is occurring in MS?

Answer 17

Chronic MS includes periventricular lymphocytes, macrophages and TH1 and TH17 cells.
Activated Macrophages is the cause for demyelination

Question 18

What infectious agents can trigger Multiple Sclerosis?

Answer 18

Measles, Mumps, Rubella, and Herpes Simplex

Question 19

What is the hallmark of Multiple Sclerosis?

Answer 19

Demyelinated plaques on MRI (“Dawson fingers”)

Preference for optic nerve

Question 20

What is the demyelinating pattern for MS?

Answer 20

Focal areas of injury

Question 21

Clinical findings of Multiple Sclerosis patients.

Answer 21

Symptoms of the brainstem, optic nerves or spinal cord affecting both sensory and motor neurons,

Optic neuritis
Extremity weakness, ataxia or numbness

Question 22

What lab tests can be done to help diagnose multiple sclerosis?

Answer 22

Spinal Tap will show mild increase in protein and oligoclonal bands of IgG.

EMG potentials of nerves will show decreased conduction

Question 23

What is the cause of death for Multiple Sclerosis?

Answer 23

Respiratory paralysis or UTI while in terminal coma

Question 24

How do Multiple Sclerotic lesions differ from that of abscesses and neoplasms?

Answer 24

Focal lesions (similar to abscesses and neoplasms)
The enhanced ring will be faint, often incomplete without surrounding vasgenic edema.

There will be NO neovasculature
There will be NO angiogenesis
There will be NO necrosis

Question 25

Describe Devic disease?

Answer 25

Also known as neuromyelitis optica Presents as bilateral optic neuritis and spinal cord involvement (optic neuritis and myelitis). It is a more destructive lesion than in multiple sclerosis. Also involves grey matter

Question 26

Who gets neuromyelitis optica?

Answer 26

Predominantly the Asian Population

Question 27

Describe signs and symptoms of Devic syndrome.

Answer 27

Optic neuritis may manifest as visual impairment with decreased visual acuity. Myelitis dysfunction can lead to muscle weakness, reduced sensation, or loss of bladder and bowel control.

Question 28

Patient comes in presenting with headache and lethargy. He states he recently had gotten a viral immunization 2 weeks ago. His symptoms progress and he slips into a coma and dies. What condition did he most likely have?

Answer 28

Acute disseminated encephalomyelitis

Question 29

Patient comes in with acute headache and lethargy but on the H&P she has no focal findings. Her PMx indicates two weeks ago she had a viral infection. She completely recovers. What is something she might have had.

Answer 29

Acute dissemniated encephalomyelitis

Question 30

describe Central pontine myelinolysis

Answer 30

A loss of myelin causing lesion of the basis pontis.Cause by a rapid correction of hyponatremia. This causes a rapidly developing quadraplegia.

Question 31

Who is at risk of develope central pontine myelinosis?

Answer 31

Alcoholics Malnourished - Severe electrolyte/osmolar imbalances Orthopic liver trasnplants

Question 32

A man comes into the ER. He quickly falls into a coma and dies. On autopsy it is revealed that his corpus callosum and anterior commissure have become necrotic. What is the probable cause of the syndrome and what is it called?

Answer 32

He alcoholic and suffered from a rare demyelination disease called Marchiafava - Bignami

Question 33

What is cause by a Thiamine deficiency?

Answer 33

A Beri Beri or a Wernicke Encephalopathy

Question 34

Patient presents with Ataxia, opthalmaplegia and nystagmus. The patient is an alcoholic. What does this disease progress into without proper nutrition supplements?

Answer 34

This is a case of Wernicke's encephalopathy caused by a Thiamine (B1) deficiency. Treatment is to give the patient Thiamine. Progression is to Wernicke - Korsakoff syndrome which will include memory defects

Question 35

Patient comes into the ER having problems with gait, and double vision. He appears unstable during walking and has nystagmus. You have to lave to see another patient but return later. During the initial visit the patients was Alert with a GC of 15. But now the patient cannot remember the exam or you were. What is the diagnosis and the treatment?

Answer 35

The patient has developed Wernicke-Korsakoff syndrome. Give thiamine supplements

Question 36

What are some symptoms of alcohol withdrawal?

Answer 36

``` Delirium tremens (DT's) a state of confusion and visual hallucinations Agitation Fever Convulsions Black outs ```

Question 37

What is the pathology related to alcohol withdrawal?

Answer 37

Focal hemorrhages/necrosis in the mammillary bodies Early there will be dilated capillaries that allow the infiltration of macrophages. The macrophages will cause cysts containing hemosiderin.

Question 38

Compare Vit B1 to vit B12

Answer 38

Wernicke's encephalopathy is a reversible condidtion whereas Vit B12 deficiency can potentially have irreversible effects on the nervous system.

Question 39

What are some symptoms of Pernicious anemia?

Answer 39

B12 deficiency can cause numbness, tingling and slight ataxia in the lower extremity. May progress to spastic weakness and complete paraplegia.

Question 40

Describe the Pathogenesis of Pernicious anemia

Answer 40

Swelling of the myelin produces vacoules that begin in the mid thoracic level and cause the demyelination of the lateral and posterior columns. This causes loss vibratory, propioceptive and discriminative touch below in addition to UMN signs of the lower extremities. This is called Subacute Combined Degeneration of the Spinal cord.

Question 41

Patient comes in with numbness, burning sensations in the lower extremities and difficulting walking. He says he is an alcoholic that recently stopped drinking because he started losing feeling in his lower legs. Physical exam reveals marked weakness in both lower limbs and hyperreflexia. Upper extremities are normal. What condition does the patient have?

Answer 41

Subacute Combine Degeneration of the Spinal cord (SCDSC) give them B12 injections

Question 42

A mother is recently pregnant and as her OB you remind her one of the things she should avoid is fish. What conditions can occur in her child if she avoids your advice?

Answer 42

Fish consumption can possibly cause Mercury poisoning. Mercury acts similarly to Alzheimers in that neurofibrillary tangles form due to the binding of mercury to the tubulin molecules for microtubule formation. This process occurs spefically in the cerebellar granule cells. Methylmercury is the main culprit and it is not cleared by kidneys and shows increase uptake in brain