Demyelinating Diseases (Martin) Flashcards
Multiple sclerosis (MS)
autoimmune demyelinating disorder of white matter with relapsing and remitting episodes of variable duration; symptoms are separated in time and space;
What are the genetic factors associated with multiple sclerosis (MS)?
DR2 and IL-2 and IL-7
Histology of a patient with multiple sclerosis (MS) in the active plaque phase?
foamy macrophages that contain lipid rich PAS+ debris; preservation of axons of oligodendrocytes
CSF examination finding for a patient with multiple sclerosis (MS)?
elevated IgG (oligoclonal IgG bands - gamma region)
mildly elevated proteins
pleocytosis
Neuromyelitis optica (NMO)
AKA Devic’s Disease
bilateral optic neuritis and spinal cord demyelination; antibody against aquaporins; treatment with plasmapheresis
What is the antibody in Neuromyelitis optica (NMO)?
against aquaporins
What is the treatment for Neuromyelitis optica (NMO)?
Plasmapheresis; to decrease the antibody burden
Acute Disseminated Encephalomyelitis (ADEM)
diffuse monophonic demyelinating disease that follows a viral infection (or viral immunization); patients present with headache, lethargy and coma (20%) die
What do patients with Acute Disseminated Encephalomyelitis (ADEM) typically present with?
headache, lethargy and coma (20%) die
Acute Disseminated Encephalomyelitis (ADEM) typically following what kind of infection?
a viral infection or viral immunization
Central Pontine Myelinolysis
AKA Osmotic demyelination syndrome
loss of myelin WITHOUT inflammation; present with “locked in syndrome” (acute paralysis, dysphagia and loss of consciousness); 2-6 days after rapid correction of hyponatremia
Overcorrection of what electrolyte imbalance can lead to Central Pontine Myelinolysis?
hyponatremia
disease characterized by trinucleotide glutamate repeats that form a mutated protein
Huntington’s Disease
disease characterized by an accumulation of AB plques and tangles
Alzheimer’s Disease
Alzheimer’s Disease
AD; common cause of dementia; global cortical atrophy (predominately the parietal lobes); will develop hydrocephalus ex vacuo (filling up the empty space); deposition of amyloid plaques and neurofibrillary tangles
What is the most common cause of dementia in the elderly?
Alzheimer’s Disease
Which lobes is predominately affected in Alzheimer’s disease?
the parietal lobes
Deposition of what is characteristically significant in Alzheimer’s disease?
amyloid plaques and neurofibrillary tangles
Tangles are aggregates of which protein?
tau
amyloid plaques are aggregates of which peptide?
alpha-beta peptides derived from the amyloid precursor protein (APP)
Histology of neuritic (senile) plaques?
amyloid core - seen on a congo red stain (different from APP)
Histology of diffuse plaques?
no amyloid core (differentiate from neuritic plaques)
Tangles or plaques correlate better with degree of dementia a patient is experiencing?
number of tangles (more tangles = more severe)
Histology of AD?
amyloid plaques and neurofibrillary tangles and Hirano bodies - glassy eosinophilic bodies (actin)
Hirano bodies
seen in Alzheimer’s disease; elongated glassy eosinophilic bodies made predominately of actin
Frontotemporal Lobar Degenerations (FTLDS)
tau inclusions (no alpha-beta plaques); most common disorder is Pick Disease - progressive dementia involving the frontal and temporal lobes only
Pick Disease
a type of Frontotemporal Lobar Degenerations (FTLDS); early onset with alterations in personality (frontal lobes) and language (temporal) with sparing of the posterior 2/3 of superior temporal temporal gyrus; “knife-edge” thin gyri
Which gyri of the temporal lobes is spared in Pick Disease?
posterior 2/3rds of superior temporal gyrus
“knife-edge” thin gyri is characteristic for which pathology?
Pick Disease
Progressive Supranuclear palsy (PSP)
akinetic rigid syndrome (slow and stiff); progressive truncal rigidly; common in men; fatal within 5-7 years of onset; has widespread neuronal loss
What is the clinical syndrome of Pakinsonism?
Diminished facial expression “masked facies”
Slowness
Festinating gait
Rigidity
“pill-rolling” tremor (resting)
Parkinson Disease (PD)
AD with alpha synuclein accumulation and mut on chromosome 4q21; loss of dopaminergic neurons in the substantial nigra; responsive to L-deopa;
patients with Parkinson’s disease have an accumulation of what?
alpha synuclein
Where is the mutation in a patient with Parkinson’s disease that encodes alpha synuclein?
chromosome 4q21
patients with juvenile Parkinson’s disease have what mutation?
AR with mutations in PARKIN
Which mutation is the most common cause of AD Parkinson’s disease?
LRRK2
Dementia with leeway bodies
- dementia develops first (before and PD signs)
- both dementia and movement symptoms are present at time of diagnosis
- dementia symptoms appear within one year after movement symptoms
Corticobasal degeneration (CBD)
akinetic rigid syndrome with progressive taupathy - tau will be positive in gray and white matter; will see cognitive decline
What is the most specific pathological finding in CBD?
tau-positive threads in gray and white matter
Multiple system atrophy (MSA)
sporadic disorder with alpha-synuclein inclusions in oligodendrocytes; triad -
1. striatonigral circuit (Parkinsonism)
2. ataxia
3. autonomic dysfunction (orthostatic hypotension)
Huntington Disease (HD)
AD movement disorder and dementia; jerky hyperkinetic movement (chorea); polyglutamine trinucleotide (CAG) repeats chromosome 4p16.3 encoding the GOF Huntington protein;
Disease that has CAG repeats
Huntington Disease (HD)
Genetic inheritance of Huntington Disease (HD)?
AD; (CAG) repeats chromosome 4p16.3 encoding the GOF Huntington protein
How does paternal transmission play a significant role in Huntington’s disease?
Anticipation; spermatogenesis leads to an earlier onset via paternal transmission
Which part of the part is most severely impacted in Huntington’s disease?
the caudate nucleus
Friedrich’s Ataxia
AR with GAA trinucleotide repeats on chromosome 9q13 encoding the Frataxin protein; progressive ataxia, weakness and COD usually due to cardiomyopathy
What is the inheritance of Friedrich’s ataxia?
AR with GAA trinucleotide repeats on chromosome 9q13 encoding the Frataxin protein
What is the typically cause of death of someone with Friedrich’s ataxia?
cardiomyopathy
Ataxia-Telangiectasia
AR syndrome with mutated ATM gene on chromosome 11q22-q23 that begins in childhood; triad
1. telangiectasia
2. ataxia
3. immunodeficiency
Amyotrophic lateral sclerosis (ALS)
loss of both upper and lower motor neurons; begins in the 50s; neurons contain Bunina bodies (PAS+ inclusions); patient will report of dropping objects (muscle weakness) and cramping of arms and legs
“Bunina bodies” are typically seen in which disorder?
Amyotrophic lateral sclerosis (ALS)
Patient is in her 50s and complains of sudden habit of dropping of items and experiences muscle weakness in arms and legs, what should you suspect?
Amyotrophic lateral sclerosis (ALS)
Kid is perfectly fine until 1 yrs old and presents with deficiency of Hexosaminidase A and accumulation of GM2 gangliosides
Tay-Sachs; cherry red spot in maculae
Tay-Sachs
Hex A gene on chr 15; deficiency of Hexosaminidase A and accumulation of GM2 gangliosides; kid is perfectly fine until 1 yrs old; cherry red spot in maculae
Krabbe disease
deficiency in galactocerebroside B-galactosidase; rapidly progressive; onset 3-6 months and death by 2 yrs; loss of myelin and oligodendroglia; will see aggregation of macrophages “globoid cells”
Disease with unique diagnostic feature of “globoid cells”
Krabbe disease; deficiency in galactocerebroside B-galactosidase; onset 3-6 months and death by 2 yrs
Metachromatic Leukodystrophy
AR on chromosome 22q; deficiency in arylsulfatase A; accumulation of Cerebroside sulfate; motor symptoms death 5-10 years
Adrenoleuodystrophy
x-linked rec ABCD1 gene; loss of myelin, gloss and lymphocytic infiltration; young boy who presents with behavioral changes and adrenal insufficiency
A young boy who presents with behavioral changes and adrenal insufficiency should make you suspect which disorder?
Adrenoleuodystrophy; x-linked rec ABCD1 gene
Disease with x-linked rec inheritance and mutation on the ABCD1 gene?
Adrenoleuodystrophy; loss of myelin, gloss and lymphocytic infiltration; young boy who presents with behavioral changes and adrenal insufficiency
“Tigroid pattern”
Pelizaeus-Merzbacher disease; x linked invariably fatal leukodystrophy
What is the inheritance of mitochondrial encephalopathies?
inheritance only through maternal lines (mom gives to all offspring)
What are the 4 pathologies with the mitochondrial inheritance pattern?
- Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS)
- Myoclonic Epilepsy & Ragged Red Fibers (MERRF)
- Leigh Syndrome
- Kearn-Sayre Syndrome
Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS)
most common disease caused by mitochondrial inheritance pattern; mut MTTL1; muscle involvement and lactic acidosis; stroke-like episodes that do NOT correspond with specific vascular territories
Myoclonic Epilepsy & Ragged Red Fibers (MERRF)
mitochondrial inheritance pattern; myoclonus, seizure disorder and evidence of myopathy; ragged red fibers on histology
Leigh Syndrome
mitochondrial inheritance pattern; lactic acidemia, seizures and hypotonia; death within 1-2 years; brain will have spongiform appearance with vascular proliferation
Kearn-Sayre Syndrome
mitochondrial inheritance pattern; ataxia, pigmentary retinopathy and cardiac conduction defects
