Neuro - Pathology (Demyelinating/Dysmyelinating disorders & Adrenoleukodystrophy)

Question 1

What processes are occurring in multiple sclerosis?

Answer 1

Autoimmune inflammation and demyelination of CNS (brain and spinal cord).

Question 2

What are the 5 main components of presentation that can be seen in multiple sclerosis patients?

Answer 2

Patients can present with (1) optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils), (2) Internuclear ophthalmoplegia, (3) Hemiparesis, (4) Hemisensory symptoms, or (5) Bladder/bowl incontinence.

Question 3

Describe (very briefly) the course of multiple sclerosis.

Answer 3

Relapsing and remiting course

Question 4

In what patient population is multiple sclerosis most common? In which racial/ethnic group is multiple sclerosis more common?

Answer 4

Most often affects women in their 20s and 30s; More common in whites

Question 5

What CSF finding characterizes multiple sclerosis?

Answer 5

Increased protein (IgG) in CSF. Oligoclonal bands are diagnostic.

Question 6

What imaging modality is the gold standard for multiple sclerosis? What are 2 major imaging findings that may be seen?

Answer 6

MRI is gold standard; (1) Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with destruction of axons. (2) Multiple white matter lesions separated in space and time

Question 7

What are 3 main methods of treatment for multiple sclerosis? What are 3 additional symptomatic treatments?

Answer 7

(1) Beta-interferon (2) Immunosuppression (3) Natalizumab; Symptomatic treatment for (1) neurogenic bladder (catheterization, muscarinic antagonists), (2) spasticity (baclofen, GABA receptor agonist), (3) pain (opioids)

Question 8

What is the most common variant of Guillain-Barre syndrome?

Answer 8

Acute inflammatory demyelinating polyradiculopathy.

Question 9

What is Acute inflammatory demyelinating polyradiculopathy?

Answer 9

Autoimmune condition that destroys Schwann cells –> inflammation and demyelination of peripheral nerves and motor fibers

Question 10

What are 3 categories of deficits to associate with acute inflammatory demyelinating polyradiculopathy?

Answer 10

(1) Results in symmetric ascending muscle weakness/paralysis beginning in lower extremities. (2) Facial paralysis in 50% of cases. (3) Autonomic function may be severely affected (e.g., cardiac irregularities, hypertension, or hypotension).

Question 11

Describe the survival rate and recovery time of patients with Acute inflammatory demyelinating polyradiculopathy.

Answer 11

Almost all patients survive; the majority recover completely after weeks to months

Question 12

What is the CSF finding associated with Acute inflammatory demyelinating polyradiculopathy? What physical sign is also found in Acute inflammatory demyelinating polyradiculopathy, and what causes it?

Answer 12

Findings: Increased CSF protein with normal cell count (albuminocytologic dissociation); Increased protein –> papilledema

Question 13

Name 2 infections with which acute inflammatory demyelinating polyradiculopathy is associated. Explain this association.

Answer 13

Associated with infections (Campylobacter jejuni and CMV) –> autoimmune attack of peripheral myelin due to molecular mimicry, inoculations, and stress, but no definitive link to pathogen.

Question 14

What intervention is critical until recovery of Acute inflammatory demyelinating polyradiculopathy patients? What are 2 additional treatments?

Answer 14

Respiratory support is critical until recovery; Additional treatment: Plasmapharesis, IV immune globulins.

Question 15

What is the name of the classic triad of MS? What symptoms are included in this triad?

Answer 15

Charcot classic triad of MS is a SIN: Scanning speech, Intention tremor (also Incontinence and Internuclear ophthalmoplegia), Nystagmus.

Question 16

What is Progressive multifocal leukoencephalopathy (PML)?

Answer 16

Demyelination of CNS due to destruction of oligodendrocytes.

Question 17

With what pathogen is Progressive multifocal leukoencephalopathy associated?

Answer 17

Associated with JC virus.

Question 18

In what patient population is PML seen, at what percentage of this population, and why?

Answer 18

Seen in 2-4% of AIDS patient (reactivation of latent viral infection)

Question 19

Describe the progression and prognosis of PML.

Answer 19

Rapidly progressive, usually fatal.

Question 20

What drug is associated with increased risk of PML?

Answer 20

Increased risk associated with natalizumab.

Question 21

What is another name for Acute disseminated encephalomyelitis? What characterizes this condition?

Answer 21

Acute disseminated (postinfectious) encephalomyelitis; Multifocal perivenular inflammation and demyelination after infection (commonly measles or VZV) or certain vaccinations (e.g., rabies, smallpox)

Question 22

Name 2 infections and 2 vaccines associated with Acute disseminated (postinfectious) encephalomyelitis.

Answer 22

Infections: (1) Measles (2) VZV; Vaccines: (1) Rabies (2) Smallpox

Question 23

What kind of disease is Metachromatic leukodystrophy, and what mode of inheritance does it have? What is the most common cause of it?

Answer 23

Autosomal recessive lysosomal storage disease, most commonly due to arylsulfatase A deficiency

Question 24

What is the underlying pathophysiology of Metachromatic leukodystrophy?

Answer 24

Buildup of sulfatides –> impaired production of myelin sheath

Question 25

What are physical exam findings associated with metachromatic leukodystrophy?

Answer 25

Findings: Central and peripheral demyelination with ataxia, dementia

Question 26

What is another name for Charcot-Marie-Tooth disease?

Answer 26

Also known as hereditary motor and sensory neuropathy (HMSN).

Question 27

Define Charcot-Marie-Tooth disease.

Answer 27

Group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath.

Question 28

What is the mode of inheritance of Charcot-Marie Tooth disease? What are 2 physical findings associated with it?

Answer 28

Typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches)

Question 29

What kind of disease is Krabbe disease? What is its pathogenesis?

Answer 29

Autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase. Buildup of galactocerebroside and psychosine destroys myelin sheath.

Question 30

What are 4 findings associated with Krabbe disease?

Answer 30

Findings: (1) Peripheral neuropathy (2) Developmental delay (3) Optic atrophy (4) Globoid cells

Question 31

What type of disorder is Adrenoleukodystrophy, and what patient population does is typically affect?

Answer 31

X-linked genetic disorder typically affecting males

Question 32

What is the pathogenesis of Adrenoleukodystrophy?

Answer 32

Disrupts metabolism of very-long-chain fatty acids –> excessive buildup in nervous system, adrenal gland, and testes

Question 33

What are 2 complications to associate with the course of Adrenoleukodystrophy?

Answer 33

Progressive disease that can lead to long-term coma/death and adrenal gland crisis