Demyelinating, Neurodegenerative And Genetic Disorders Flashcards
What are demyelinating diseases?
Acquired conditions, preferentially damage myelin with relative preservation of axons
What are degenerative diseases?
Diseases of gray matter; progressive loss of neurons with associated secondary changes in white matter tracts; presence of protein aggregates that are resistant to degradation through ubiquitin proteasome system
How are degenerative diseases classified?
Asymptomatic/anatomic (anatomic regions affected reflect sx) or pathologic (types of inclusions or abnormal structures observed)
What is the clinical pattern for prion disease?
Rapidly progressive dementia
What are the inclusions for prion disease?
Kuru plaques and diffuse PrP deposits
What is the genetic cause for prion disease?
PrP
What is the clincal pattern for Alzheimer’s disease?
Dementia
What are the inclusions for Alzheimer’s disease?
Amyloid beta plaques and tau tangles
What are genetic causes of Alzheimer’s?
APP, PS1 and 2, trisomy 21
What is the clinical pattern for frontotemporal degeneration (FTLD)?
Behavioral changes, language disturbance
What inclusions are seen in FTLD?
tau, TDP43, FUS
What are the genetic causes for FTLD?
Tau, TDP43, progranulin, C9orf72, FUS
What is the clinical pattern for PD?
Hypo kinetic movement disorder with or without dementia
What inclusions are associated with PD?
Alpha synuclein, or none
What are the genetic causes of PD?
Alpha synuclein (mutations or amplification), LRRK2, DJ1, PINK1, parkin
What is the clincal pattern for PSP?
Parkinsonism with abnormal eye movements
What inclusions are seen in PSP?
Tau (also the genetic cause)
What is the clinical pattern for CBD?
Parkinsonism with asymmetric movement disorder
What inclusion is seen with CBD?
Tau
What is the clinical pattern for multiple system atrophy?
Parkinsonism, cerebellar ataxia, autonomic failure
What inclusion is seen in MSA?
Alpha synuclein
What is the clinical pattern for HD?
Hyperkinetic movement disorder
What inclusion is seen with HD?
Huntington (Htt is genetic cause)
What is the clinical pattern for spinocerebellar ataxia?
Cerebellar ataxia
What inclusions are seen with spinocerebellar ataxias?
Various porteins (polyglutamine containing)
What is the clinical pattern for ALS?
Weakness with upper and lower motor neuron signs
What inclusions are seen with ALS?
SOD1, TDP43, FUS (also genetic causes)
What is the clinical pattern for spinal bulbar muscular atrophy?
Lower motor neuron weakness, diminished androgen
What inclusions are seen with SBMA?
Androgen receptor (polyglutamine containing); androgen receptor also genetic cause
What are neurofibrillary tangles?
Bundles of filaments in cytoplasm of neurons that displace or encircle nucleus (not specific to AD unlike plaques)
What kind of neurofibrillary tangles are present in pyramidal neurons?
Flame tangles
What kind of neurofibrillary tangles are present in the round nucelus?
“Globose”, basket weave or fibers around nucleus
Basophilic fibrillar structures can be seen with which stain?
Bielschowsky stain (silver stain)
What kind of neurofibrillary tangles are present after death?
Ghost or tombstone tangles
What is tau?
Abnormally hyper phosphorylated, axonal microtubule associated protein that enhances microtubule assembly —> forming tangles (MAP2 and ubiqutin)
What is MPTP?
Illegal psychoactive meperidine analogues (heroin) —> acute Parkinsonism and destruction of neurons in the substantia nigra
What are neuronal storage diseases?
Mostly autosomal recessive; defect in catabolism of sphingolipids, mucopolysaccharides or mucolipids; accumulation of substrate of enzymes in lysosomes (neuronal death); cortical involvement includes loss of cognitive function and possible seizure activity
What are leukodystrophies?
Mostly AR except adrenoleukodystrophy is X linked; loss of cerebral function at younger ages; myelin abnormalities; diffuse involvement of white matter (deterioration of motor skills, spasticity, hypotonia or ataxia)
What are mitochondrial encephalopathies?
Oxidative phosphorylation disorders (generation of ATP, neurons critically dependent on it); mutations in mitochondrial or nuclear genomes; selectively target neurons
What is heteroplasmy?
Presence of both wild type and mutated mitochondrial genomes within different populations of mitochondria in single cells —> wide cell to cell variation in disease expression
