Neurodegeneration and Neurodegenerative Diseases Flashcards
Neurodegeneration
Progressive loss (death) of neurons beyond that of the normal aging process.
It is a problem because neurons cannot be replaced.
What is the most important risk factor for the common neurodegenerative diseases?
Age
Causes of neurodegeneration
- Neurodegenerative diseases
- Cancer
- Trauma (head/spine injury)
- Viral diseases/Infections
- Vascular/Circulatory disorders.
- Developmental disorders
Examples of vascular and circulatory disorders that can cause neurodegeneration
Strokes
Narrowing of blood vessels (atherosclerosis)
Thrombosis
etc.
Venous infarction
Usually results from venous sinus thrombosis
Risk factors include states that result in hyperviscosity or increased coagulability
Generally they are very hemorrhagic
Flow gradient
Heterogenous regional blood flow (CBF) reduction after focal ischemia
Densely ischemia
Region surrounded by areas of less severe CBF reduction
Ischemic penumbra
An area of reduced perfusion sufficient to cause potentially reversible clinical deficits but insufficient to cause disrupted ionic homeostasis
Pathophysiology of ischemic brain injury
At the start the area of penumbra is large, but as time goes by without treatment this becomes infarction
Infections that can cause Neurodegeneration
- Meningitis – infection of the blood vessel membrane of the brain
- Cerebral abscess
- Subdural empyema
- Viral encephalitis
- Cerebritis
What do dementive diseases cause?
The loss of mental faculties
What makes dementive diseases special?
Often the cause is unknown
No cure
Progressive and irreversible
Types of neurodegenerative diseases
Dementia
Movement disorders
Motor neuron disease (ALS)
Dementias
Alzheimer’s disease: common, amyloid hypothesis, plaques and tangles, gross brain atrophy
Prion disease: rare, “transmissible” protein, rapidly progressive, vacuolar changes
Movement disorders
Parkinson’s disease: hypokinetic, loss of dopaminergic cells substantia nigra, Lewy bodies
Huntington’s disease: choreiform movements, caudate atrophy, nuclear inclusions
Motor Neuron Disease (ALS)
Loss of upper and lower motor neurons, progressive over 2-5 years
Time Course for a ND patient
Develop minor psychological/behavioural or motor issues (50 years)
Begin differential diagnosis (may take a year)
Early treatment aimed at quality of life/diet/exercise
Treatments to delay symptoms (Years)
Treatments to alleviate worsening symptoms (Years)
Patient’s symptoms become severe (palliative care)
Patient dies from secondary disease eg pneumonia
Polio
Poliomyelitus is caused by an RNA virus, the poliovirus
Enters the CNS in 3% of cases and in 1% leads to focal loss of motoneurons in the spinal cord.
Rostra-caudal/medio-lateral topographical map
Study of spinal motoneuron loss in polio and comparison to the resulting loss of muscle control
It allowed mapping of motoneuron foci in the spinal cord to the innervated muscle
Amyloidogenic diseases
Neurodegenerative diseases where there is deposition of an abnormal protein isoform.
These aggregates can be inside or outside of the cell
E.g: Alzheimer’s, Parkinson’s, Prion diseases
Prion diseases
Very rare
Experimentally transmissible
Human and animal diseases are fairly similar, so animal models are useful.
Generally due to mutations in the prion protein
Characteristics of prion diseases
- Long incubation period of infection (10-40 years)
- Deposition of large amounts of abnormal prion protein
- Rapid neuronal loss
- Gliosis
- Vacuoles
- Short symptomatic period (6-18 months)
Metal hypothesis
AD, PD and Prion disease are all linked to a protein that occurs normally in the brain
In each case the protein binds copper.
In each case there is a suggestion that metals play some role in the cause (either iron or copper).
Demyelinating diseases
Acquired disorders of myelin, such as multiple sclerosis
Dismyelinating diseases
Genetic disorders of myelin and its turnover, such as leukodystrophies
Possible causes of ND
Aggregates - toxicity
Inflammation - microglia going wrong
Oxidative stress - tau
Mitochondrial damage
Multiple Sclerosis
Most common disease of CNS myelin
CNS myelin is selectively destroyed (axons are relatively preserved)
Typical progression of MS
Onset usually 30-40 years old
Disease is typically progressive with relapsing and remitting accumulations of focal neurologic deficits.
Frequently intermittent
Etiology of MS
Autoimmune
Protective cells attack rather than defend
Symptoms of MS
- muscle weakness
- Difficulty moving – ataxia
- Difficulty with speech or swallowing
- Pain
- Depression
- Cognitive disturbances
