Exam 1: Myelin and Metabolic Disorders Flashcards Preview

My Neuroanatomy Behavioral Neurosciences > Exam 1: Myelin and Metabolic Disorders > Flashcards

Flashcards in Exam 1: Myelin and Metabolic Disorders Deck (57)
Loading flashcards...
1
Q

Review – Myelin disorders: Autoimmune

Name the 4 autoimmune diseases/problem/issues that are related to mylelin disorders

A

—1) Multiple Sclerosis (CNS)

——2) Acute disseminated encephalomyelitis (acute) and acute hemorrhagic encephalomyelitis (hyperacute) (both CNS)

—3) Neuromyelitis optica

4) —Guillain-Barré (PNS)

2
Q

Review – Myelin disorders: —Metabolic

Name a Metabolic diseases/problem/issues that is related to mylelin disorders

A

—Central pontine myelinolysis —(rapid correction of hyponatremia/osmotic shock),

Marchiafava-Bignami

3
Q

Review – Myelin disorders: Leukodystrophy

*Genetic/storage diseases (—Often due to catabolic enzyme deficiency)*

Name the 3 Leukodystrophy diseases/problem/issues that are related to mylelin disorders

A

—1) —Krabbe

——2) Metachromatic leukodystrophy (—accumulation of sulfatides)

—3) —Adrenoleukodystrophy (accumulation of very long chain fatty acids),

Pelizaeus-Merzbacher (proteolipid protein gene),

Canavan (Aspartylcyclase activity )

4
Q

Review – Myelin disorders: ——Nutritional

Name a Nutritional diseases/problem/issues that is related to mylelin disorders

A

—Subacute Combined Degeneration of the Spinal Cord - Vitamin B12 Deficiency – degeneration of posterior, lateral, and other columns (PNS and CNS)

5
Q

Review – Myelin disorders: —

—Myelin disorders can be Dysmyelination or Demyelination.

1) How does each one affect myelin?
2) What types of disorders are releated to each?

A

—Faulty myelin production** (_Dys_myelination**)

  • —Genetic
  • ——Metabolic

—Attack on normal myelin (Demyelination)

  • ——Immunologic
  • ——Toxic/environmental/nutritional/metabolic
  • ——Infectious
  • ——Other
6
Q

Review – —Myelin is produced in? —

—

A

—CNS by the oligodendroglial cells

—PNS by Schwann cells

7
Q

Review – —Myelin: —

_____ axons

—Allows _____ conduction of axonal impulses

—Composed of _____ and _____

A

Review – —Myelin: —

—Insulates axons

—Allows saltatory (i.e. faster) conduction of axonal impulses

—Composed of lipids and proteins

8
Q

Review – ——Loss of myelin leads to?

A

—• Short-circuits

—• Slowing of conduction

• —Failure of bodily functions

9
Q

Multiple Sclerosis summarys - Etiology:

What is the basic etiology of MS?

A

autoimmune disease (immunologic)

10
Q

Multiple Sclerosis - Cellular immunity:

—Initiated by _____ cells react against _____ _____

—TH1 lymphocytes secrete _____ (IFN-γ) that activate _____ which injure myelin

—TH17 lymphocytes promote recruitment of _____

—• Plaques (lesions) contain _____ and _____

A

Multiple Sclerosis - Cellular immunity:

• —Initiated by CD4+ T cells react against self myelin

—TH1 lymphocytes secrete cytokines (IFN-γ) that activate macrophages which injure myelin

—TH17 lymphocytes promote recruitment of leukocytes

—• Plaques (lesions) contain macrophages** and **T-lymphocytes (mostly CD4+)

11
Q

Multiple Sclerosis - Cellular immunity:

• —Antibodies also present with uncertain role

—_____ bands seen on CSF electrophoresis

___-cells present

A

Multiple Sclerosis - Cellular immunity:

• —Antibodies also present with uncertain role

—Oligoclonal bands seen on CSF electrophoresis

—B-cells** present

*—Pathogenetic evidence of infection; —HumanHerpesvirus-6 antibodies are seen in ~40%

**—B-cell depletion can decrease incidence of demyelinating diseases

12
Q

Multiple Sclerosis - —Risk factors/Pathogenesis:

• ——Familial risk

—15-fold increase with _____ relative

—Higher incidence (150-fold) with _____ twins

—• ——Genetic linkage

—___-hapotype of MHC

—Siblings with MS may share same _____ receptor haplotype

A

Multiple Sclerosis - —Risk factors/Pathogenesis:

—• ——Familial risk

—15-fold increase with 1st-degree relative

—Higher incidence (150-fold) with monozygotic twins

—• ——Genetic linkage

—DR2-hapotype of MHC

—Siblings with MS may share same T-cell receptor haplotype

13
Q

Multiple Sclerosis - —Risk factors/Pathogenesis:

—• ——Weiner

—single-nucleotide polymorphisms (SNPs) associated with a higher risk of developing MS were identified on the interleukin-___ receptor a gene, interleukin-___ receptor a gene, and confirmed in the ___-___ locus.

—• ——Populations

—More common in _____ populations in northern latitudes

——Arguments of _____ factors

A

Multiple Sclerosis - —Risk factors/Pathogenesis:

—• ——Weiner

single-nucleotide polymorphisms (SNPs) associated with a higher risk of developing MS were identified on the interleukin-2 receptor a gene, interleukin-7 receptor a gene, and confirmed in the HLA-DRA locus.

—• ——Populations

—More common in Caucasian populations in northern latitudes

—Possibly accounts for increased incidence in temperate latitudes (vs. equator)

—Arguments of environmental factors

—Migration studies show that risk can change with moves early in life.

14
Q

Multiple Sclerosis - —Pathogenesis:

—• ———Infections (particularly early in life) may cause breakdown of _____ and entry of lymphocytes into _____

——• _____ antibodies in ~40% of MS patients

—• _____ and ____ have also been suggested as a potential triggers

A

Multiple Sclerosis - —Pathogenesis:

—• Infections (particularly early in life) may cause breakdown of BBB and entry of lymphocytes into CNS (no agent has been conclusively established)

——• Human HerpesVirus-6 antibodies in ~40% of MS patients – more than EBV and CMV

—• ——EBV and Chlamydia have been suggested as a potential triggers

15
Q

Multiple Sclerosis - Clinical:

—• ————Often begins with _____ nerve involvement (_____ neuritis)

——• Often _____ and _____ course

——• Female-to-Male ratio is ___:1

——• Rarer before ___ and after___

——• _____ seen on MR

——• High _____-signal

A

Multiple Sclerosis - —Clinical:

—• ————Often begins with optic nerve involvement (—Optic neuritis); —May or may not proceed to MS – only 10 to 50% develop MS.

——• Often remitting and relapsing course

——• Female-to-Male ratio is ~2:1

——• Rarer before 20 and after 50

——• Lesions seen on MR

——• High T2-signal

—

16
Q

Multiple Sclerosis - Clinical: lesion deficits

Multiple lesions produce variety of deficits.

(I dont think we need to memorize these as much as understand what all can be affected. )

—Visual, —Spinal Cord, —Cerebellar deficits, Lhermitte sign, —Intranuclear ophthalmoplegia and other eye movement disorders, —Depression and psychiatric conditions, and many other findings

A

Multiple Sclerosis - —Clinical: lesion deficits

—Visual: —Intranuclear ophthalmoplegia, —Pupillary abnormalities, —Nystagmus

—Spinal Cord: —Acute transverse myelitis (spinal cord). —Paralysis, —Sensory loss (dorsal columns), —Bladder control dysfunction

—Cerebellar deficits: —Ataxia, —Scanning speech, —Intention tremor

—Lhermitte sign: Shocklike feeling with neck flection

—Intranuclear ophthalmoplegia and other eye movement disorders

—Depression and psychiatric conditions

—Many other findings

—

17
Q

Multiple Sclerosis - Pathology: (Gross)

_______ in _____ matter of brain and spinal cord

—• Loss of _____ matter – _____ in areas that should be _____

—• In brain, often adjacent to _____ ventricles

—Firmer than adjacent areas – _____

—• Can show “_____” due to microscopic perivascular pattern

A

Multiple Sclerosis - —Pathology: (Gross)

Lesions (plaques) in white matter of brain and spinal cord (CNS)

—• Loss of white mattergrey-tan lesions in areas that should be white

—• In brain, often adjacent to lateral ventricles

• —Firmer than adjacent areas – gliosis

—• Can showfingers” due to microscopic perivascular pattern

18
Q

Multiple Sclerosis - Pathology: (—Micro)

acute (active), inactive, and shadow plaques

—Acute (active) plaques

_____ attacking and engulfing myelin

—_____, often ___vascular

—_____ apoptosis

A

Multiple Sclerosis - —Pathology: (—Micro)

acute (active), inactive, and shadow plaques

—Acute (active) plaques

—Macrophages attacking and engulfing myelin

—Inflammation** (lymphocytes and macrophages), often **perivascular

—Oligodendroglial apoptosis

19
Q

Multiple Sclerosis - Pathology: (—Micro)

acute (active), inactive, and shadow plaques

—Inactive plaques

—Loss of myelin with fewer _____ cells

—_____ of oligodendroglial cells

—Gliosis

—Relative _____ of axons

A

Multiple Sclerosis - —Pathology: (—Micro)

acute (active), inactive, and shadow plaques

—Inactive plaques

—Loss of myelin with fewer inflammatory cells

—Reduction of oligodendroglial cells

—Gliosis

—Relative preservation of axons (vs. myelin loss)

—Some axonal loss possible

20
Q

Multiple Sclerosis - Pathology: (—Micro)

acute (active), inactive, and shadow plaques

—Shadow plaques

—Evidence of _____ – axons with thin myelin

A

Multiple Sclerosis - —Pathology: (—Micro)

acute (active), inactive, and shadow plaques

—Shadow plaques

—Evidence of remyelinationaxons with thin myelin

21
Q

What disorder is shown in the image?

What are we supposed to know about this image?

A

Multiple Sclerosis

The area around the occipital horns of the lateral ventricle should be myelinated white matter.

22
Q

What disorder is shown in the image?

What are we supposed to know about this image?

A

Multiple Sclerosis

The Luxol Fast Blue is used in MS sections; Luxol Fast Blue stains myelin blue.

The higher-power images show loss of myelin with relative preservation of axons (i.e. c/w demyelination).

23
Q

What disorder is shown in the image?

What are we supposed to know about this image?

A

Multiple Sclerosis

Note the presence of multiple lesions. The characteristicDawson’s Fingersare areas of demyelination adjacent to the ventricles (Fig. A).

Figure E shows a high cervical lesion and a lesion in the corpus callosum.

24
Q

Multiple Sclerosis - Pathology: CSF

—_____ bands (_____ antibodies) on immunoelectrophoresis

—Glucose _____

Protein _____

WBC slightly to moderately _____

A

Multiple Sclerosis - —Pathology: CSF

—Oligoclonal bands (IgG antibodies) on immunoelectrophoresis– antigen not exactly known

—Glucose normal

Protein normal or slightly elevated

WBC slightly to moderately elevated

*Remember the immune basis of MS.

25
Q

Multiple Sclerosis - Different courses:

—Relapsing remittingRelapses followed by Improvement after _____ (remission); _____ progression (most common)

—Secondary progressiveFollows relapsing, remitting - _____ progression _____ remissions (i.e. remissions less common)

—Primary progressiveGradual progression _____ remissions

—Relapsing progressive – _____ but still accumulate disability

A

Multiple Sclerosis - —Different courses:

—Relapsing remitting – Relapses followed by Improvement after attacks (remission); little or slow progression (most common)

—Secondary progressiveFollows relapsing, remitting - Steady progression with or without remissions (i.e. remissions less common)

—Primary progressiveGradual progression without remissions

—Relapsing progressiveRemissions but still accumulate disability

26
Q

Multiple Sclerosis - Variable course:

—

  • ——dependent on form, severity, locations
  • ——Untreated remitting/relapsing30% disability in _____ years from onset
A

Multiple Sclerosis - —Variable course:

  • —dependent on form, severity, locations
  • ——Untreated remitting/relapsing30% disability** in **20-25 years from onset

—

27
Q

Multiple Sclerosis - Therapy:

—Emphasizes the _____ nature of MS (examples below)

***—Immunomodulators: _____-beta, —_____zumab***

—Corticosteroids: —_____prednisolone

—Immunosuppressors: —_____trone (inhibits topoisomerase, induces crosslinks and strand breaks), —_____phosphamide

—Other: —Treatment of a variety of symptoms including —fatigue and psychiatric

A

Multiple Sclerosis - —Therapy:

—Emphasizes the immune/autoimmune nature of MS (examples below)

***—Immunomodulators: —Interferon-beta, —Natalizumab***

—Corticosteroids: —Methylprednisolone

—Immunosuppressors: Mitoxantrone (inhibits topoisomerase, induces crosslinks and strand breaks), —Cyclophosphamide

—Other: —Treatment of a variety of symptoms including —fatigue (Amantadine, CNS Stimulants. Baclofen for spasticity) and psychiatric

28
Q

Devic disease/Neuromyelitis Optica:

Variants/Related Disease of _____?

seen more in _____, higher _____ : _____ ratio

•— Has antibodies against _____, major water component of astrocytes; areas of demyelination show loss of _____

•— _____ optic neuritis and _____ spinal cord involvement

•— Greater _____ matter involvement; _____ can be present

— Plasmaphoresis or depletion of _____ with anti-___ antibody

• —NMO-IgG is available per Weiner and is used in _____

A

Devic disease/Neuromyelitis Optica:

*** Variants/Related Disease of Multiple Sclerosis ***

seen more in —Asians, higher women : male ratio

•— Has antibodies against aquaporin-4, major water component of astrocytes; areas of demyelination show loss of aquaporin -4

—Bilateral optic neuritis** and **prominent spinal cord involvement

—Greater grey matter involvement; necrosis can be present

• —Plasmaphoresis or depletion of B-cells with anti-20 antibody

• —NMO-IgG is available per Weiner and is used in diagnosis

29
Q

—Acute MS – Marburg form:

Variants/Related Disease of _____?

seen more in _____ individuals

—• _____ course

—• _____ plaques

A

—Acute MS – Marburg form:

*** Variants/Related Disease of Multiple Sclerosis ***

• seen more in younger individuals

—• Fulminant course

—• Large plaques

30
Q

—A classic MRI image is shown:

Where are the lesions?

What would be the likely histopathological appearance of these lesions?

What would be the most likely initial lesion/symptom in such a patient?

*These are post-mortem MR scans. There is no fluid within the ventricular system.

A

—A classic MRI image is shown:

Where are the lesions?

What would be the likely histopathological appearance of these lesions?

What would be the most likely initial lesion/symptom in such a patient?

*These are post-mortem MR scans. There is no fluid within the ventricular system.

31
Q

Acute Disseminating Encephalomyelitis:

——Follows _____ or _____

• ——Occurs within _____ after infection (_____ course than MS)

—• —_____ symptoms (examples?) vs. focal symptoms of MS

• ——(rapid or slow?) progress

• ——Pathology: —Myelin loss with relative _____ of axons, Neutrophils _____, —_____phasic

• ——Possibly _____ autoimmune reaction to myelin

A

Acute Disseminating Encephalomyelitis:

• —Follows viral infection or immunization

—• —Occurs within a week or two after infection (faster course than MS)

—• —General symptoms (headache, lethargy, coma) vs. focal symptoms of MS

——Rapid progress20% fatal; remainder have complete recovery

• ——Pathology: —Myelin loss with relative preservation of axons, —Neutrophils early**, —_Mono_phasic**

——Possibly acute autoimmune reaction to myelin

32
Q

Acute Hemorrhagic Encephalomyelitis:

———age groups normally affected?

—• ———Follows ______ ______ illness (—_____ ______ in some)

—• ———_____ in many patients

—• ———_____venular demyelination.

—• ———_____ destructive than ADEM. —destruction of _____ vessels. —Necrosis of _____ matter. —Acute hemorrhage, _____ deposition, and _____ in less severely damaged areas

—• ———Possibly _____ autoimmune reaction to myelin

A

Acute Hemorrhagic Encephalomyelitis:

———Young adultsand children

—• ———Follows upper respiratory illnessMycoplasma pneumonia in some)

—• ———Fatal in many patients

—• ———Perivenular demyelination. Sometimes widely distributed and confluent

—• ———More destructive than ADEM. —destruction of small vessels. —Necrosis of white and grey matter. —Acute hemorrhage, fibrin deposition, and inflammation in less severely damaged areas

—• ———Possibly hyperacute autoimmune reaction to myelin

*tip to remember. AHE has an H in it, and its the Hyperacute rxn to myelin, vs. ADE which is an acute rxn to myelin

33
Q

Acute Disseminating Encephalomyelitis (ADE) vs.

Acute Hemorrhagic Encephalomyelitis (AHE)

What does ADE follow?

How does that differ from AHE?

A

Acute Disseminating Encephalomyelitis (ADE) vs.

Acute Hemorrhagic Encephalomyelitis (AHE)

ADE: follows —viral infection or immunization

AHE: follows —upper respiratory illness

Mycoplasma pneumonia in some)

34
Q

Acute Disseminating Encephalomyelitis (ADE) vs.

Acute Hemorrhagic Encephalomyelitis (AHE)

What is the pathology of ADE?

How does that differ from AHE?

A

Acute Disseminating Encephalomyelitis (ADE) vs.

Acute Hemorrhagic Encephalomyelitis (AHE)

pathology of ADE:

—Myelin loss with relative preservation of axons, —Neutrophils early, Monophasic

pathology of AHE:

—More destructive than ADEM

——Perivenular demyelination. Destruction of small vessels. Necrosis of white and grey matter. —Acute hemorrhage, fibrin deposition, and inflammation in less severely damaged areas

35
Q

Acute Disseminating Encephalomyelitis (ADE) vs.

Acute Hemorrhagic Encephalomyelitis (AHE)

ADE is a _____ autoimmune reaction to myelin while AHE is a _____ autoimmune reaction to myelin

A

Acute Disseminating Encephalomyelitis (ADE) vs.

Acute Hemorrhagic Encephalomyelitis (AHE)

ADE is a acute autoimmune reaction to myelin while AHE is a hyperacute autoimmune reaction to myelin

36
Q

Central Pontine Myelinolysis (CPM)

—• Thought to occur with _____ correction of _____natremia (_____ sodium) – osmotic shift

——• Alternative – extreme _____-osmolality or other _____ imbalance

—• —Loss of myelin with _____ axon preservation: —Central _____ pontis. —Pontine _____. —Can occur _____tentorially

——• Rapidly progressive _____; ”_____ syndrome”

——• Seen in _____, _____nourished conditions, severe electrolyte or osmotic imbalance, or in liver transplantation

A

Central Pontine Myelinolysis (CPM)

——• Thought to occur with rapid correction of hyponatremia (low sodium) – osmotic shift

***You must correct severe hyponatremia in a slow, deliberate manner!!!***

——• Alternative – extreme hypo-osmolality or other metabolic imbalance

——• Loss of myelin with relative axon preservation: —Central basis pontis. —Pontine tegmentum. —Can occur supratentorially

—Rapidly progressive quadriplegia; ”locked-in syndrome

— Seen in alcoholism, malnourished conditions, severe electrolyte or osmotic imbalance, or in liver transplantation

37
Q

Buzz words:

Rapidly progressive quadriplegia

locked-in syndrome

hyponatremia followed by IV hypertonic saline

If you see these buzzwords consider?

A

Buzz words:

Rapidly progressive quadriplegia

locked-in syndrome

hyponatremia followed by IV hypertonic saline

Central Pontine Myelinolysis (CPM)

38
Q

Marchiafava-Bignami

—Myelin loss/necrosis in and around _____ _____ and _____ ______

— Classically thought to occur in _____ of _____ heritage

—Abuse of _____ (contaminant?)

—History of _____ and poor nutrition with overlap with other syndromes (—_____-_____, —Alcoholic _____ dysfunction)

A

Marchiafava-Bignami

• —Myelin loss/necrosis in and around corpus callosum and anterior commissure

—Classically thought to occur in alcoholics of Italian heritage

—Abuse of cheap Italian red wine (contaminant?)

—History of alcoholism and poor nutrition with overlap with other syndromes (—Wernicke-Korsakoff, —Alcoholic cerebellar dysfunction)

39
Q

Progressive Multifocal Leukoencephalopathy (PML)

———Result of infection with _____.

—• ———_____ cells are infected.

—• ———_____ results. See LFB-stained image.

—• ———Astrocytic abnormalities are also present.

—• ———PML is often an _____ infection.

A

Progressive Multifocal Leukoencephalopathy (PML)

———Result of infection with JC virus.

—• ———Oligodendroglial cells are infected.

—• ———Demyelination results. See LFB-stained image.

—• ———Astrocytic abnormalities are also present.

—• ———PML is often an opportunistic infection.

40
Q

Leukodystrophy

————_____ defects

—• ————Affects _____ or _____ of components of myelin

  • —————Often a _____ disease with buildup of substrate due to problems with _____ enzyme
  • —————Substrate can be shuttled to alternative pathway with _____ _____

—• ————Often autosomal _____

A

Leukodystrophy

Genetic defects

—• ————Affects production or handling of components of myelin

—• ————Often a storage disease with buildup of substrate due to problems with catabolic enzyme

—• ————Substrate can be shuttled to alternative pathway with toxic byproducts

—• ————Often autosomal recessive

41
Q

Sphingolipidoses

This is a _____ pathway.

• An absent or abnormal _____ leads to _____ of substrate, which can harm the cell by direct or indirect means.

A

Sphingolipidoses

  • This is a catabolic pathway.
  • An absent or abnormal enzyme leads to build up of substrate, which can harm the cell by direct or indirect means.
42
Q

Krabbe Disease

form of _____dystrophy

—Sphingolipidosis

—• Deficiency of _____ β-galactosidase; required for conversion of galactocerebroside to ceramide and galactose. —Galactocerebroside can _____.

—• Most problems thought to be from?

—• Galactosylsphingosine is producedtoxic to _____ cells

A

Krabbe Disease

  • form of Leukodystrophy
  • Sphingolipidosis

—• Deficiency of galactocerebroside β-galactosidase; required for conversion of galactocerebroside to ceramide and galactose. —Galactocerebroside can accumulate.

—• Most problems thought to be from shifting galactocerebroside to alternative pathway

—• Galactosylsphingosine**** is producedtoxic** to **oligodendroglial cells

43
Q

Krabbe Disease

—• Onset ___-___ months; Survival uncommon beyond ___ years

• —Clinicallymotor signs, —Stiffness and _____, —Worsening problems with _____

—• Loss of myelin in _____ with characteristic _____ cells (very enlarged multinucleated _____) in CNS clustered around _____; severe _____

A

Krabbe Disease

—• Onset 3-6 months; Survival uncommon beyond 2 years

• —Clinicallymotor signs, —Stiffness and weakness, —Worsening problems with feedings

—• Loss of myelin in PNS and CNS with characteristic globoid cells (very enlarged multinucleated macrophages) in CNS clustered around blood vessels; severe gliosis

44
Q

Buzz words:

Globoid” cells

If you see these buzzwords consider?

A

Buzz words:

“Globoid” cells

Krabbe Disease

Much of the white matter is gray/yellow because of the loss of myelin. Inset picture: “Globoid” cells are the hallmark of the disease.

45
Q

Metachromatic Leukodystrophy

—Deficiency of arylsulfatase A which cleaves _____ for _____-containing lipids; Accumulation of _____ (galactosyl _____)

—• Myelin breakdown

—• Infantile, juvenile, and adult forms; —InfantileDeath by ___-___ years (most common); —AdultSlower course

  • —Therapy – _____ _____ transplantation
  • —Pathology; —_____ demyelination _____ gliosis; —Vacuolated macrophages in _____ matter and _____; —Vacuoles contain _____tides

—Metachromatic – shift absorptive spectrum of dyes – toluidine blue and cresyl violet

—Diagnosis – Can identify in _____

A

Metachromatic Leukodystrophy

—Deficiency of arylsulfatase A which cleaves sulfate for sulfate-containing lipids; Accumulation of sulfatides (galactosyl sulfatide)

—• Myelin breakdown

—• Infantile, juvenile, and adult forms; —InfantileDeath by 5-10 years (most common); —AdultSlower course

  • —Therapybone marrow transplantation
  • —Pathology; —Striking demyelination with gliosis; —Vacuolated macrophages in white matter and PNS; —Vacuoles contain sulfatides

—Metachromatic – shift absorptive spectrum of dyes – toluidine blue and cresyl violet

—Diagnosis – Can identify in urine

46
Q

Adrenoleukodystrophy (Several forms)

——___-linked form

—• ——Mutations in _____ gene on Xq28

  • ———Inability to _____ very-long chain fatty acids (VLCFA’s) within _____
  • ———VLCFA’s _____ – toxic affects
  • ———Myelin loss in _____ matter (with sparing of the immediate _____ _____) with gliosis and lymphocytic _____

—

A

Adrenoleukodystrophy (Several forms)

• ——X-linked form

—• ——Mutations in ALD gene on Xq28

  • ———Inability to catabolize very-long chain fatty acids (VLCFA’s) within peroxisomes
  • ———VLCFA’s accumulatetoxic affects
  • ———Myelin loss** in **deep white matter (with sparing of the immediate subcortical U-fibers) with gliosis and lymphocytic inflammation
47
Q

Pelizaeus-Merzbacher

——___-linked

—• Gene encodes _____ protein

—• Myelin _____ in cerebral hemispheres but some areas remain producing _____ appearance

—• Early signs: _____ eye movements, _____tonia, choreoathetosis, and pyramidal signs

—• Late signs: _____, _____, ataxia

A

Pelizaeus-Merzbacher

• ——X-linked

—• Gene encodes proteolipid protein (PLP)

—• Myelin almost completely lost** in **cerebral hemispheres but some areas remain producing tigroid appearance

—• Early signs: Peduncular eye movements, hypotonia, choreoathetosis, and pyramidal signs

—• Late signs: spasticity, dementia, ataxia

48
Q

Subacute combined Degeneration of Spinal Cord

—Deficiency of vitamin _____

—• —Loss of myelin with _____ in posterior columns, corticospinal and other tracts

—• —_____ and axonal loss can occur

—• —Symptoms: —Begins with slight _____, numbness and tingling in _____ extremities. —Can progress to _____ weakness and total _____

A

Subacute combined Degeneration of Spinal Cord

• —Deficiency of vitamin B12

—• —Loss of myelin with vacuolization in posterior columns, corticospinal and other tracts

—• —Gliosis and axonal loss can occur

—• —Symptoms: —Begins with slight ataxia, numbness and tingling in lower extremities. —Can progress to spastic weakness and total paraplegia

49
Q

—Vitamin B1 (Thiamine) deficiency

• ——_____-_____ Syndrome

——Often seen in _____ with poor _____

—• Early Clinical: Psychoses and _____plegia acutely —

Late Clinical: —Memory disturbances and _____

—• Midline lesions****mamillary bodies, thalamus, periventricular regions; —_____ early; _____ late

_____ leading to atrophy/cystic change in affected areas

—• Treatment; —_____ administration (_____ to glucose); —Correction of other nutritional deficits

A

—Vitamin B1 (Thiamine) deficiency

  • ——Wernicke-Korsakoff Syndrome
  • ——Often seen in alcoholics with poor nutrition

—• Early Clinical: Psychoses and ophthalmoplegia acutely —

Late Clinical: —Memory disturbances and confabulation

—• Midline lesionsmamillary bodies, thalamus, periventricular regions; —Hemorrhagic early; hemosiderin late

—Necrosis leading to atrophy/cystic change in affected areas

—• Treatment; —Thiamine administration (prior to glucose); —Correction of other nutritional deficits

50
Q

—Hepatic Encephalopathy

—Pathogenesis:

—Follows _____ dysfunction

—Altered _____ in the central nervous system and neuromuscular system

—Elevated blood _____ level and other toxins promote generalized brain _____.

—Clinical:

—Disturbances in _____ (subtle to coma/death)

—Fluctuating neurologic signs including _____, _____reflexia, and particularly asterixis (i.e. _____ movements)

—_____ if clinical condition is addressed

—Pathology:

—Few gross changes (outside of edema)

—Alzheimer Type ___ _____ develop – enlarged, folded, cleared nuclei

*Note the lobulated and enlarged _____ nucleus in the lower portion of the photograph

A

—Hepatic Encephalopathy

—Pathogenesis:

—Follows liver dysfunction

—Altered neurotransmission in the central nervous system and neuromuscular system

—Elevated blood ammonia level and other toxins promote generalized brain edema.

—Clinical:

—Disturbances in consciousness (subtle to coma/death

—Fluctuating neurologic signs including rigidity, hyperreflexia, and particularly asterixis (i.e. flapping movements)

—Reversible if clinical condition is addressed

—Pathology:

—Few gross changes (outside of edema)

—Alzheimer Type 2 astrocytes develop – enlarged, folded, cleared nuclei

*Note the lobulated and enlarged astrocyte nucleus in the lower portion of the photograph

51
Q

——Carbon monoxide

——Results in _____ discoloration of skin

—• ——Global hypoxic changesnecrosis of layers ___ and ___ of cortex, hippocampus cerebellar _____ cells

—• ——___lateral necrosis of _____ pallidus

A

——Carbon monoxide

• —— ——Results in cherry–red discoloration of skin

—• ——Global hypoxic changesnecrosis of layers III and V of cortex, hippocampus, cerebellar Purkinje cells

—• ——Bilateral necrosis of globus pallidus

In picture: Carbon monoxide poisoning. (a) Hemorrhagic discoloration (arrows) of the pallidum in acute carbon monoxide poisoning. The dorsal part of the nucleus is most severely affected. (b) and (c) Examples of symmetric (b) and asymmetric (c) cavitation of the dorsomedial part of the pallidum in survivors of acute carbon monoxide poisoning. Note the ill-defined gray discoloration of the cerebral white matter and thinning of the corpus callosum in (c). (d) Cavitated necrosis (arrows) in the cerebral white matter in a survivor of acute carbon monoxide poisoning. (e) The frontal white matter has a gelatinous gray appearance and is focally cavitated in the brain from a long-term survivor of carbon monoxide poisoning. The arcuate fibers are spared.

52
Q

———Methanol

———Degeneration of _____ ganglion cells

• ————___lateral _____ necrosis; focal _____ matter necrosis

A

—Methanol

  • ———Degeneration of retinal ganglion cells
  • ————Bilateral putamenal necrosis; focal white matter necrosis
53
Q

————Ethanol

————Degeneration of _____-_____ cerebellar _____

—• ————Clinical – _____ ataxia

—

Other Pathology – Ethanol-related (emphasize) including Marchiafava Bignami ——Cerebellar Degeneration, —Wernicke-Korsakoff, ——Myopathy and Neuropathy, Fetal Alcohol Syndrome, —Hepatic Encephalopathy

A

——Ethanol

• ————Degeneration of anterior-superior cerebellar vermis

—• ————Clinicaltruncal ataxia

—

Other Pathology – Ethanol-related (emphasize) including Marchiafava Bignami ——Cerebellar Degeneration, —Wernicke-Korsakoff, ——Myopathy and Neuropathy, Fetal Alcohol Syndrome, —Hepatic Encephalopathy

54
Q

—————Methotrexate and/or Radiation

—————Necrosis around _____

—• —————Axonal _____

—• —————Radiation can also lead to widespread necrosis

A

—Methotrexate and/or Radiation

• —————Necrosis around ventricles or vessels

—• —————Axonal spheroids

—• —————Radiation can also lead to widespread necrosis

55
Q

A 50 yo man has ataxia secondary to chronic alcohol abuse**. Imaging of his **cerebellum shows atrophy. What part of the cerebellum is most likely to be atrophic?—————

A. Anterior-superior Vermis

B. Posterior-inferior Vermis

C. Lateral

D. Tonsils

A

A 50 yo man has ataxia secondary to chronic alcohol abuse**. Imaging of his **cerebellum shows atrophy. What part of the cerebellum is most likely to be atrophic?—————

A.

Anterior-superior Vermis

56
Q

A 35 year-old died 10 years after resection** of her **terminal ileum** due to **Crohn disease. A spinal cord section is shown. What is the etiology?

A. Chronic aluminum toxicity

B. Thiamine deficiency

C. Vitamin A toxicity

D. Vitamin B12 deficiency

E. Vitamin D deficiency

A

A 35 year-old died 10 years after resection of her terminal ileum due to Crohn disease. A spinal cord section is shown. What is the etiology?

D.

Vitamin B12 deficiency

57
Q

Fill in this table

A

Fill in this table

Decks in My Neuroanatomy Behavioral Neurosciences Class (32):