LEC-3 Neuropathology (1) Flashcards
Hypoxia/Ischemia results in degeneration of what neurons?
Hippocampus
Huntington’s Disease results in degeneration of what neurons?
Caudate Nucleus
Parkinson’s Disease results in degeneration of what neurons?
Substantia Nigra
Amyotrophic lateral sclerosis (ALS) results in degernation of what neurons?
Motor Neurons
What are the signs of Acute Neuronal Injury?
- Red neurons (eosinophilic neuronal necrosis)
- Dark & smudgy chromatin
- Hypoxic/ischemic injury
- Eosinophilic, shunken cytoplasm
- Cell death is by necrosis or apoptosis
Myelin disorders are associated with what component of the nervous system?
Oligodendrocytes
What component of the nervous system is most resistant to injury?
Astrocytes
What are the major mechanisms of cellular injury?
- Free radical injury
- Excitotoxic injury
- Excitatory amino acids: Glutamate and aspartate
- Excitatory amino acid receptors: NMDA receptor
- Depolarization
Describe the excitotoxic injury.
Inappropriate activation of NMDA receptor that results in:
- Membrane depolarization
- Calcium influx
- Mitochondrial dysfunction
What does subacute/chronic neuronal injury result in?
- Degeneration (take longer than acute neuronal injury)
- Cell loss is hard to see early on; reactive glial changes is best indication
- Cell death is mainly due to apoptosis
What is the axonal reaction?
- Changes that occur in the neuron cell body in response to axonal injury
- Regenerate attempt
What are the features of the axonal reaction?
- Central chromatolysis
- Damage to axon
- Margination of Nissil substance
- Central clearing of the cytoplasm
- Peripheral displacement of the nucleus
- Rounding of the cell body
What is this image?
Red Neuron
What is this image?
Axonal reaction
What is this image?
Axonal spheroid
Axons are highlighted as black lines with what stain?
Silver
What inclusions are associated with Parkinsons?
Lewy body
What inclusion is associated with Alzheimers?
Neurofibrillary tangles
What inclusions are associated with Pick’s Disease?
Pick’s body
Fronto-temporal lobar degernation
Neuronal inclusions may occur as a manifestation of aging, when there are intracytoplasmic accumulations of complex lipids (___________).
Lipofuscin
Abnormal cytoplasmic deposition of complex lipids and other substances also occurs in ___________________________ in which substrates or intermediates accumulate.
genetically determined disorders of metabolism
Viral infection can lead to abnormal intranuclear inclusions, as seen in __________.
Herpetic infection
Viral infection can lead to abnormal cytoplasmic inclusions, as seen in _______.
Rabies. (Negri body)
Viral infection can lead to abnormal nuclear AND cytoplasmic inclusions, as seen in _______
Cytomegalovirus (CMV) infection
Abnormal vacuolization of the perikaryon and neuronal cell processes in the neuropil is seen in what disease?
Creutzfeldt-Jacob disease
What is Trans-synaptic degeneration?
- Secondary degeneration of a neuron connected to a dying neuron
- Anterograde or retrograde
What is this image and what is it diagnostic of?
- Alzheimers Glia Type II
- Hyperammonemia
What is this image and what is it diagnostic of?
- Creutzfeldt astrocyte
- Not diagnostic of any specific disease; just a reactive astrocyte
- Commonly seen in demyelinating disease
What is this image and what is it diagnostic of?
- Satellitosis (satelliting)
- Diagnostic of oligodendroglial changes
What is this image and what is it diagnostic of?
- Onion Bulb Schwaan Cell
- Diagnostic of Charcot-Marie-Tooth Disease
What is this image?
Large Group Neurogenic Atrophy
What is the cause of Myasthenia Gravis?
Auto-antibodies against ACh-receptors at neuromuscular junction
What are the symptoms of Myasthenia Gravis?
Progressive weakness throughout the day (feel fine in the morning, can’t physically keep eyes open by nighttime)
What are associated disorders of Myasthenia Gravis?
- Other autoimmune disorders
- Thymoma/thymic hyperplasia
What is the cause of Lambert-Eaton Syndrome?
Auto-antibodies against voltage-gated Calcium channels at axon terminal, inhibiting release of NT-filled vesicles following an action potenial
What is this image?
Muscular dystrophy
What does this image show?
- Mitochondrial disease
- Ragged red fiber
What is this image show?
Polymyositis: Endomysial inflammation and atrophy
What is the cause, symptoms, and pathology associated with Polymyositis?
- Cause: CD8+ mediated attack on muscle cells
- Symptoms: Diffuse pain
- Pathology: Intrafascicular inflammation
What does this image show?
Dermatomyositis: Extrafascicular inflammation and perifascicular atrophy
What is the cause, symptoms, and pathology associated with Dermatomyositis?
- Cause: Antibody-mediated attack on muscle cells
- Symptoms: Diffuse pain and rash
- Pathology: Extrafascicular inflammation; perifascicular atrophy
What does this image show?
Inclusion Body Myositis: Rimmed vacuole (with faint blue dots)
What is the cause, symptoms, and pathology associated with Inclusion Body Myositis?
- Cause: Degenerative
- Symptoms: Steroid resistance
- Pathology: Inclusions; rimmed vacuoles
What is the cause of Duchenne Muscular Dystrophy?
Dystrophin deficiency due to X-linked frameshift mutation of gene
Onset: 5-6 years, death in adolescence or yound adulthood
What is Becker Muscular Dystrophy?
A milder form of Duchenne MD due to a point mutation in the dystrophin gene
What are congenital myopathies?
Fixed, structural defects in muscle
Weakness at brith, nonprogresssive
Names after histological appearance:
- Central core
- Rod body
- Centronuclear
What does this image show?
Central core myopathy
What does this image show?
Rod body myopathy
What does this image show?
Centronuclear myopathy
What is the onset of Multiple Sclerosis (MS)?
> 50 years
What are the symptoms of of Multiple Sclerosis (MS)?
- Seeminly random
- Episodic losses of neural function (vision problems, weakness in arm, parasthesia in leg)
- Increased Ig levels in CSF
What is the cause of Multiple Sclerosis (MS)?
Auto-immune attack of myelin (mainly CD4+ and macrophage mediated)
What is associated with the acute phase of Multiple Sclerosis (MS)?
- Demyelination
- Lots of immune cells near axons
What is associated with the chronic phase of Multiple Sclerosis (MS)?
- Reactive astrocytosis
- Axon loss
What is the cause of Devic Disease (Neuromylitis Optica)?
Autoantibodies against Aquaporin-4 receptors
What are the symptoms of Devic Disease (Neuromylitis Optica)?
Simultaneous blindness and paraplegia
What is the onset of Acute Disseminated Encephalomyelitis (ADEM)?
A few weeks post-infection/vaccination
What is the cause of Acute Disseminated Encephalomyelitis (ADEM)?
Possibly a cross-reaction with or autoimmunity against myelin
What symptoms are associated with Acute Disseminated Encephalomyelitis (ADEM)?
Rapid onset of headache, lethargy, coma
What is the onset of Acute Necrotizing Hemorrhagic Encephalomyelitis (ANHE; Weston-Hurst Disease)?
Shortly after UTI or M. pneumoniae infection
What is associated with Infectious Demyelination?
- HIV
- Progressive multifocal leukoencephalopathy (PML)
What is Marchiafava-Bignami?
Demyelinating disorder that is associated with a lesion of the corpus callosum
Also associated with alcoholism
What is Demyelinating pseudotumor (tumefactive demyelination)?
Demyelinating disorder that has a single mass lesion that mimics a neoplasm; moderate correlation between this and the patient developing MS later on
What is Central Pontine and Extrapontine Myelinolysis (CPM; osmotic demyelination syndrome)?
Primary demyelinating disease with a lesion that appears at the base of pons or any location where white and gray matter closely associate (so, most of hindbrain/parts of midbrain)
- Associated with rapid correction of electrolye imbalance
