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Neuromusculoskeletal & Psychiatry II Exam #2 > Demyelinating, Neurodegenerative, Genetic and Toxic Diseases > Flashcards

Demyelinating, Neurodegenerative, Genetic and Toxic Diseases Flashcards

1
Q

What CNS diseases are considered entirely “acquired”?

Which ones are considered “inherited”?

A

Demyelinating diseases

Leukodystrophies

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2
Q

What is needed for the diagnosis of MS?

What are the common presenting neurological signs and symptoms? (4)

10-50% of patients with what disease will develop MS?

A

Distinct episodes of neurologic defects, separated in time and are attributable to white matter lesions that are separated in space.
Relapsing and remitting episodes of variable duration.

UL visual impairment
Ataxia
Nystagmus
Motor and sensory impairments

Optic neuritis

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3
Q

What is the genetic link of MS susceptibility?

What are receptor genes involved?

A

DR2

IL-2, IL-17

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4
Q

What is the immunological pathogenesis of MS?

What cells are mainly found in the plaque infiltrate?

A

CD4+, Th-1 and Th-17 cells that cross-react with self-myelin antigens.
Th-1 cells secrete IFN-y
Th-17 cells recruit WBCs

T cells, mainly CD4+.

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5
Q

What is effected most in the brain in MS? Where is it found most?

How does it appear grossly?

A

White matter; adjacent to lateral ventricles and near optic n.

Multiple well-circumscribed, slightly depressed irregularly shaped plaques that are sclerotic (firm).

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6
Q

What stain is used to find MS plaques?

A

Luxol fast blue myelin stain

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7
Q

What is meant by “active plaque” in MS histology?

A

Abundant macrophages containing lipid-rich, PAS+ myelin, debris.

There is relative preservation of axons within plaque and depletion of oligodendrocytes.

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8
Q

What is inactive plaque in MS?

What is shadow plaque?

A

Inactive: quiescent plaques with disappearing inflammation.

Shadow: plaque found between normal and affected white matter and is NOT sharply circumscribed.

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9
Q

What are the clinical CSF findings for MS? (4)

A

Mildly elevated protein
Moderate pleocytosis (1/3 of cases)
IgG increased
Oligoclonal IgG bands (gamma region)

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10
Q

What occurs in Neuromyelitis Optica?

What is found in the CSF?

What antibody is linked to this disease?

What is the treatment?

A

Synchronous bilateral optic neuritis and spinal cord degeneration.

Neutrophils and turbid appearance.

Antibody to aquaporins (damage integrity of BBB).

Decrease antibody burden via plasmaphoresis.

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11
Q

What does Acute Disseminated Encephalomyelitis (ADEM) cause?

What is the cause of the disease?

What is the presentation?

What is the morphology?

A

Perivenous encaphalitis.

Monophasic demyelinating disease that follows either a viral infection, or rarely viral immunization.

1-2 wks. post infection. Presents with HA, lethargy and coma.

Myelin loss with relative preservation of axons.

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12
Q

What is Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE)?

Who is most likely to be affected?

What occurs before this onsets?

What is the outcome?

A

Fulminant syndrome of CNS demyelination.

Young adults and children.

Recent URI.

Fatal in most cases; significant deficits in most survivors.

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13
Q

What occurs in Central Pontine Myelinosis?

What symptoms are seen?

What is the major concern?

What is the treatment?

A

Loss of myelin in a roughly symmetric pattern involving the basis pontis and portions of the pontine tegmentum.
-myelin loss without evidence of inflammation.

Acute paralysis, dysphagia, diploplia and loss of consciousness.

Overly rapid correction of hyponatremia! Severe electrolyte/osmolar imbalance.

Orthotopic liver transplant.

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14
Q

Degenerative diseases are diseases of:

What is a classic histologic feature of these diseases?

A

Gray matter, causing progressive loss of neurons.

Protein aggregates that are resistant to degredation.

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15
Q

What are the following classic molecular changes/accumulations are seen in the following degenerative diseases?

Huntington’s disease
Alzheimer’s disease
Parkinson’s disease

A

Huntington’s disease - polyglutamine repeats
Alzheimer’s disease - A-beta peptide derived from larger precursor protein
Parkinson’s disease - alpha-synclein

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16
Q

How many cases of AD are considering sporadic vs. familial?

A

Sporadic: 90%
Familial: 5-10%

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17
Q

What gross change to the brain is seen as a whole in AD?

A

Cortical atrophy - widening of sulci (frontal, temporal and parietal lobes)

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18
Q

Where are neuritic (senile) plaques seen in AD?

Where are diffuse plaques seen in AD?

What amyloid species are seen in each?

A

Neuritic: hippocampus, amygdala, neocortex.
Congo red stain (APP)
A-beta-40 and A-beta-42.

Diffuse: superficial cortex, basal ganglia and cerebellar cortex.
A-beta-42.

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19
Q

Down syndrome can cause early onset AD. Which plaques are more common?

A

Diffuse plaques

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20
Q

What histological feature is seen in AD?

What stain is used to view the basophilic fibrillary structures?

Which tangles are resistant to clearance in vivo?

A

Neurofibrillary tangles - no specific to AD!

Bielschowsky stain (silver stain)

“Ghost” or “tombstone” tangles.

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21
Q

What is a better correlation with the degree of dementia: amount of tangles or amount of plaques?

A

Amount of tangles!

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22
Q

What is granulovacuolar degeneration? What disease is it associated with?

What are Hirano bodies?

A

Small clear vacuoles with argyrophilic granules. They are normal findings in the aging brain, but are elevated in AD.

Elongated glassy eosinophilic bodies with increased actin. Also seen in AD.

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23
Q

What is deposited near the brain vasculature in AD?

A

Cerebral amyloid angiopathy (CAA) - A-beta 40

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24
Q

What clinical features does do Frontotemporal Dementias share?

Which diseases have tau pathology?

Which do not?

A

Progressive deterioration of language and changes in personality.

With tau: Pick disease, Progressive Supranuclear Palsy

Without tau: Vascular Dementia

25
Q

What is the major gross change of the brain in Pick Disease?

What are symptoms?

What is seen on histology?

A

Lobar atrophy with “knife-edge” gyri.

Behavioral changes (frontal lobe) and language disturbances (temporal lobe).

Pick cells - swollen cells
Pick bodies - cytoplasmic inclusions that are weakly basophilic and stain strongly with silver.

26
Q

What is the major symptom in Progressive Supranuclear Palsy?

Which ages are most common? What sex is more common?

What occurs in the brain as a result of this disease?

What is the progression?

What is seen on histology? (2)

A

Truncal rigidity with dysequilibrium and nuchal dystonia. May also present with abnormal speech, ocular disturbance and mild progressive dementia.

5th-7th decades; men are 2x more likely than women.

Widespread neuronal loss.

Globose neurofibrillary tangles
4R tau straight filaments

27
Q

What pathway is effected in degenerative diseases of the basal ganglia and brainstem?

A

Nigrostriatal pathway

28
Q

What are features of the clinical syndrome of Parkinson’s?

A 
Diminished facial expression
Slowness of movement
Festinating gait (short accelerated steps)
Rigidity
"Pill-rolling" tremor
29
Q

What is the treatment for PD?

A

L-dopa (immediate precursor of dopamine)

30
Q

What is the inheritance of PD?

What gene on which chromosome is mutated?

A

AD

Alpha-synuclein on chr. 4q21

31
Q

What gene is mutated in Juvenile Autosomal Rcessive PD?

A

Parkin

32
Q

What is seen on histology in PD? (2)

A

Pallor or substantia nigra and locus cereleus.

Lewy bodies - eosinophilic inclusions with a dense core surrounded by a pale halo.
-alpha-synuclein

33
Q

What inclusion is seen in Lewy body dementia (aside from Lewy bodies)?

What brain structures are spared in terms of depigmentation?

A

Lewy neurites

Cortex, hippocampus and amygdala

34
Q

What kind of disorder is Multiple System Atrophy in terms of inheritance?

What inclusions do they have?

What 3 neuroanatomic systems are involved?

A

Sporadic

Alpha-synuclein in oligodendrocytes.

  1. Striatonigral circiut (results in Parkinsonism)
  2. Olivopontocerebellar circiut (ataxia)
  3. ANS dysfunction (orthostatic hypotension)
35
Q

What 3 parts of the brain atrophy in HD?

A

Body of corpus callosum
Head of caudate nucleus
Globus pallidus

36
Q

What is the inheritance of HD?

What is genetic pathogenesis?

What neurons degenerate?

What are the major symptoms?

A

AD

Polyglutamine trinucleotide (CAG) repeat on chr. 4P16.3 causes GOF mutation in Huntingtin protein.

Medium spiny striatal neurons

Progressive movement disorder and dementia.

37
Q

What is the cause of the juvenile form of AD?

A

Anticipation - repeat expansions during spermatogenesis.

38
Q

What is the inheritance of Friedreich Ataxia?

What is the genetic pathogenesis?

What are the clinical features?

What is the usual cause of death?

A

AR (mitochondrial)

GAA repeat on chr. 9Q13 causes a LOF mutation in Frataxin protein.

Begins in the first decade with gait ataxia, clumbsiness and dysarthria, loss of DTRs, pes cavus and kyphoscoliosis.
-Cardiac arrhythmias + CHF
-DM in 10%
Wheelchair bound after 5 years of onset.

Intercurrent pulmonary infections + cardiac disease

39
Q

What is the inheritance of Ataxia-Telangiectasia?

What are features of the disease? (3)

What is the progression?

What is the genetic pathogenesis?

A

AR

Telangiectasias in CNS, conjunctiva, skin.
Lymphoid neoplasms, gliomas and carcinomas.
Immunodeficiency - recurrent sinopulmonary infections.

Death in the 2nd decade.

ATM gene is mutated on chr. 11Q-Q23 which leads to impaired removal of cells with DNA damage.

40
Q

What is the inheritance of ALS in its familial form?

What is the pathogenesis?

When does it onset?

What CNS changes are seen grossly? (3)

What histological feature is characteristic?

A

AD - mutation in SOD1 on chr. 21

Loss of LMN in spinal cord and brainstem + loss of UMN that project to corticospinal tracts. Neurogenic atrophy of skeletal muscles due to the loss of UMN.

> 5th decade

Thin anterior roots of spinal cord - decreased number of anterior horn neurons.
Atrophied precentral gyrus.

Bunina bodies = PAS + cytoplasmic inclusions

41
Q

What are the early symptoms of ALS?

What are the lasting symptoms? (4)

A

Aysmmetric weakness of hands, dropping objects, cramping, etc.

Fasciculations
Respiratory infections
Progressive muscular atrophy
Progressive bulbar palsy - deglutination and phonation problems.

42
Q

In general, what is the inheritance of neuronal storage diseases?

What do the mutations cause?

What are common symptoms?

A

AD

Defects in catabolism of sphingolipids, mucopolysaccharides or mucolipids leads to accumulation of enzyme substrate in lysosomes leading to neuronal death.

Cortical involvement - loss of cognitive function and possible seizures.

43
Q

What gene is implicated in Tay-Sachs disease?
What enzyme?

What never goes away?

What is the progression?

What is the classic sign of disease?

A

HEXA on chr. 15
Hexosaminidase A

GM2 gangliosides

Kids are fine at birth until 1 y/o, then they begin to degenerate mentally and physically until death around 2-3 y/o.

Cherry red spots in maculae

44
Q

Which mitochondrial diseases can present as muscle disease?

A

Inherited disorder of mitochondrial oxidative phosphorylation (mitochondrial encephalopathies).

45
Q

What is MELAS?

What is mutated most often?

It is the most common…

A

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.

tRNAs

Most common neurologic syndrome caused by mitochondrial abnormalities.

46
Q

What is MERRF?

What is mutated most often?

What are the symptoms?

What is seen on histology?

A

Myoclonic epilepsy and ragged red fibers.

tRNAs (distinct from MELAS)

Myoclonus, seizures and evidence of myopathy (ataxia).

Ragged red fibers.

47
Q

What is the genetic cause of Kearn-Sayre syndrome (Ophthalmoplegia plus)?

What are the 4 main symptoms?

What is seen on histology?

A

Large mitochondrial DNA deletion/rearrangement.

Cerebellar ataxia, ophthalmoplegia, pigmented retinopathy and cardiac conduction defects.

Spongiform change in gray and white matter; neuronal loss is most evident in the cerebellum.

48
Q

What is the presentation of Leigh syndrome?
What is the progression?

What is seen on histology?

A

Lactic acidemia in early childhood, seizures, feeding problems, and weakness with hypotonia.
Death within 1-2 years.

Spongiform appearance and vascular proliferation.

49
Q

What are the CNS symptoms of a vitamin B12 deficiency?

Can these be reversed with replacement therapy?

What is the pathogenesis?

A

Numbness, tingling and slight ataxia in LE. Spastic weakness of LE may ensue and lead to complete paraplegia.

Yes, unless full paraplegia has set in.

Swelling of myelin leading to vacuoles of neurons of both ascending tracts of the posterior columns and descending pyramidal tracts leads to degeneration.
This leads to subacute compined degeneration of the spinal cord.

50
Q

Symptoms of the following vitamin B1 deficiencies:

Wernicke encephalopathy

Korsakoff syndrome

Beriberi

A

Wernicke encephalopathy: acute psychotic symptoms or ophthalmoplegia (may reverse w/ thiamine).

Korsakoff syndrome: memory disturbances and confabulation (largely irreversible)

Beriberi: cardiac failure.

51
Q

What is seen on histology in Wernicke encephalopathy?

A

Foci of hemorrhage and necrosis in the mammillary bodies and walls of the 3rd and 4th ventricles.

52
Q

What areas of the brain are affected in hypo- and hyperglycemia?

A

Pyramidal neurons of Sommer’s sector of the hippocampus

Purkinje cells of cerebellum

53
Q

What pathologic change occurs in hypoglycemia?

A

Pseudolaminar necrosis

54
Q

What disease states is hyperglycemia associated with?

What is the method of treatment?

A

Ketoacidosis or hyperosmolar coma.

Gradual fluid replacement to avoid severe cerebral edema.

55
Q

What in the brain is effected due to CO poisoning? (3)

What is the major pathological process?

A

Layers III and IV of the cerebrum
Sommer’s sector
Purkinje cells

BL necrosis of the globus pallidi

56
Q

What are the 2 major pathological changes associated with methanol poisoning?

A

Degeneration of retinal ganglion cells

Selective BL putamenal necrosis

57
Q

What is atrophied in ethanol poisoning?

A

Atrophy and loss of granule cells in the anterior vermis.

Loss of Purkinje cells and proliferation of adjacent astrocytes (Bergmann gliosis).

58
Q

Which 3 CNS tumors can be induced by radiation?

What is seen on histology in radiation damage?

A

Sarcomas, gliomas and meningiomas.

Coagulative necrosis with thickened walls with intramural fibrin-like material (hyalinization).

Neuromusculoskeletal & Psychiatry II Exam #2 (15 decks)

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