Test 3: Neurological Disorders Flashcards
What is dementia?
Loss of cognitive abilities such as memory, perception, verbal ability, and judgement
What are some causes of dementia?
Vascular disorders, degenerative neuro disorders, infections, chronic drug use, types of hydrocephalus
What are mini-mental status exams used for?
Testing mental function over time. Not good for diagnosing.
What are some items that are tested on a mini-mental status exam?
Orientation, language, follow command, write a sentence, copy a picture
What are the types of dementia?
Cortical Dem- Subcortical Dem Progressive Dem Primary Dem Secondary Dem
What are the characteristics of cortical and subcortical dementia?
Cortical dem-primarily affects brain’s cortex. Causes problems with memory, language, thinking, and social behavior
Subcortical dem-affects the brain below the cortex. Causes changes in emotions and movement and problems in memory
What is the difference between primary and secondary dementia?
Primary-does not result from any other disease
Secondary-Resulted from physical disease or injury
Vascular Dementia
2nd most common type of dem after Alzheimer’s
Multiple-Infarct Dementia
- Type of vascular dem
- Caused by multiple strokes
Symptoms:
Confusion or problems with short-term memory; wandering, or
getting lost in familiar places; walking with rapid, shuffling
steps; losing bladder or bowel control; laughing or crying
inappropriately; having difficulty following instructions; and
having problems counting money
Binswanger’s disease
- Type of vascular dem
- Widespread, microscopic damage to myelin
- Causes thickening and narrowing (atherosclerosis) of arteries that feed the subcortical areas of the brain
- Rare
- Also called subcortical vascular dem
Symptoms – disruption of executive cognitive
functioning: short-term memory, organization, mood, the
regulation of attention, the ability to act or make
decisions, and appropriate behavior.
• Psychomotor slowness (e.g. increase time for fingers to turn the thought of a
letter into the shape of a letter on a piece of paper).
• Forgetfulness (but not as severe as Alzheimer’s), changes in speech,
unsteady gait, clumsiness or frequent falls, changes in personality or mood
(apathy, irritability, and depression), and urinary symptoms
Frontotemporal Dem
Originally Pick’s disease
- Type of vascular dem
- Shrinking of frontal and temporal anterior lobes
- Some cases have build up of Pick bodies in neurons (abnormal tau proteins) that cause tangles and kills cells
- 2-10% of dem cases
- about 50% have family history
Symptoms
• Behavior Change
– Impulsive, apathetic, inappropriate social behavior, distractible, change
food preferences, neglect hygiene, compulsive behavior, lack motivation
• Language Problems
– Difficulty making or understanding speech
• Spatial skills and memory remain intact
Dem with Lewy bodies
- Caused by the build up of bits of alpha-synuclein protein (Lewy bodies) inside the nuclei of neurons in neocortex and substantia nirgra
- Common type of progressive dementia (10-20% of dem cases)
- Possible relationship to Alz and Parkinson’s
• Symptoms – cognitive decline
• pronounced “fluctuations” in alertness and attention
• recurrent visual hallucinations
• parkinsonian motor symptoms (e.g. rigidity and loss of
spontaneous movement)
Alzheimer’s Disease
- Type of degenerative dem
- Cause: build up of plaques and tangles
- Includes degeneration of the hippocampus, entorhinal cortex, neocortex, nucleus basaalis, locus coeruleus, and raphe nuclei
-Symptoms– memory loss, language deterioration,
impaired ability to mentally manipulate visual
information, poor judgment, confusion, restlessness,
and mood swings
What are amyloid plaques?
- Extracelluar deposit containing a dense core of B-amyloid (AB) protein surrounding by degenerating axons and dendrites along with activated microglia and reactive astrocytes.
- Phagocytic glial cells destroy the degenerating axons and dendrites
- Caused by defective form of AB from the precursor amyloid precursor protein (APP)
Why is having the long form of B-amyloid bad?
Cells can destroy small numbers of AB42, but cannot keep up with large numbers. (Normal 5-10%, Alz around 40%)
High concentrations of AB42 fold improperly and have toxic effects on cell
Neurofibrillary tangles
Dying neurons containing intracelluar accumulations of twisted filaments of hyperphosphoryated tau protein
Abnormal filaments disrupt transport within the cell
Tangles result from excessive amounts of phosphase ions attaching to strands of tau protein changing the molecular structure
Do AB proteins or tau proteins cause Alz?
Excessive AB (not plaques) cause microglia to release toxic cytokines and trigger excessive release of glutamate from glial cells (excitotoxicity-too much Ca2+ through NMDA receptors)
Mutations of tau only produce tangles
Therefore, AB is more likely to be responsible for Alz.
Mutations of APP can result in both plaques and tangles.
What genes are associated with Alz?
- 21-gene for APP
- 1 & 14-contain presenilin genes
- Mutation of apolipoprotein E (ApoE) increases risk of late-onset Alz
Is Alz generally hereditary? What are non-genetic risk factors?
No, most are sporatic.
Strongest: TBI
Higher education level is associated with lower rates
What are preventative measures that can be taken against Alz?
Cognitive activity
Physical activity
Diet
Lifestyle
-High stress levels associated with higher risk of alz
-Sleep may help decrease AB levels
-Reduced social networks more susceptible to Alz
What treatments are available for Alz?
Acetylcholinesterase inhibitors and NMDA receptor antagonist
NSAIDs may protect from Alz
Vaccines are being tested that sensitize the immune system against AB
What is amyotrophic lateral sclerosis?
ALS/Lou Gehrig’s Disease
Degenerative disorder that attacks the spinal cord and cranial nerve motor neurons
What causes sporadic cases of amyotropic lateral sclerosis?
- Errors in RNA translation of glutamate receptor subunits in motor neurons
- (cells die from excitoxcity)
What are the symptoms of amyotrophic lateral sclerosis?
- Increased tension of muscles, causing stiff and awkward movements
- Exaggerated stretch reflex
- Progressive weakness and muscular atrophy, and finally paralysis
- Death usually occurs 5-10 years after onset due to respiratory muscle failure
- Eye control and cognitive abilities are spared
What is the treatment for amyotrophic lateral sclerosis?
Glutamate antagonist-patients live 1-3 months longer
What is multiple sclerosis (MS)?
- Autoimmune dymyelinating disease
- Myelin sheaths in CNS are attacked by a person’s immune system leaving hard patches called sclerotic plaques
- Interrupts normal neural signaling
- Symptoms are often episodic
What is the cause of MS?
The cause is unknown.
- People who spend their childhood far from the equator and are born in late winter and early spring are at most risk.
- Possibly that virus that either directly attaches to myelin or weakens BBB and allows myelin to enter general circulation which sensitized the immune system to it
What are the treatments for MS?
- Interferon B-modulates the responsiveness to the immune system
- Glatiramer acetate-stimulates interleukin 4 that suppresses immune cells
What are transmissible spongiform encephalopathies?
Misfolded prion proteins can trigger neuronal apoptosis
What causes transmissible spongiform encephalopathies?
Prions:
- Change in 3D structure of a normal protein (same amino acid sequences)
- Normal: PrPc. Infectious: PrPSc.
- Function of PrPc is unknown but possibly plays a role in synaptic function
- Could play a role in memory (mutant PRNP mice have impaired spatial memory and hippocampal LTP)
-Resistant to proteolytic enzymes and heat
How are transmissible spongiform encephalopathies transmitted?
- Infectious (diet, medical procedure, ect)
- Hereditary
What are transmissible spongiform encephalopathies characterized by?
- Loss of motor control
- Dementia
- Paralysis wasting
- Death (typically following pneumonia)
- Fatal familial insomnia presents with an untreatable insomnia
Examples of transmissible spongiform encephalopathies
- Bovine spongiform encephalopathy (mad cow disease)
- Creutzfeldt-Jakob disease
- Fatal Familial Insomnia
- Kuru
What are tumors and what are the two types?
- Mass of cells whose growth is uncontrolled and serves no useful function
- Malignant-lacks border and may metastasize (cells break off, travel through the vascular system, and grow elsewhere in the body
- Benign-cannot metastasize
How do tumors cause brain damage? Can both types cause damage?
Both types can cause damage.
Can cause compression which can directly destroy tissue or block CSF flow causing hydrocephalus (infiltration)
Do tumors arise from neurons?
No. The most serious are metastases and gliomas (derived from glial cells)
What is a seizure?
Period of sudden excessive activity of cerebral neurons
What is a convulsion? Do most seizures cause them?
Wild, uncontrollable activity of muscles if motor systems are activated.
Most seizures do not cause convulsions
What is a partial seizure? What are the two types?
Begins at a focus and remains localized.
- Simple partial seizure-doe not produce loss of consciousness
- Complex partial seizure-produces loss of consciousness
What is a generalized seizure?
Involves most of the brain
What is the most severe form of a seizure? Is it generalized or partial?
Grand mal
It is generalized.
What is the process of a grand mal seizure?
- Aura-sensation that precedes a seizure caused by excitation of neurons surrounding the seizure focus
- Neuronal firing begins at the focus and spread to surrounding regions. Then:
- Contralaterally through the corpus callosum, Basal ganglia, Thalamus, Brain stem reticular fomation
- Now symptoms begin
- Excited subcortical regions send back excitatory info to cortex, amplifying activity
- Neurons in the motor cortex fire continuously
- Tonic phase-all muscles contract forcefully and the patiet remains regid for about 15 sec
- Diencephalon sends inhibitory signals to cortex at first in brief bursts
- Clonic phase-following the tonic phase, muscles begin trembling, then start jerking convulsively, quickly at first, then slowly
- Once the inhibition wins, the patient’s muscles will relax
What are symptoms of partial seizures?
- Motor cortex-jerking movements that start in one location and move as the excitation moves along the precentral gyrus
- Occipital lobe-visual symptoms
- parietal lobe-somatosensations
- temporal lobe-hallucinations-could include old memories
- Patient may or may not loose consciousness
What is a consequence of seizures?
Can cause brain damage
- 50% of patients with seizure disorders show damage to the hippocampus
- Damage caused by excessive glutamate release
What is the most common cause of seizures?
Scarring from injury, stroke, tumor, ect
- Drugs, infections, high fever can produce seizures
- Sudden withdrawal from alcohol or barbiturates
- Up-regulation of NMDA receptors become supersensitive
What is treatment for seizures?
- Anticonvulsant drugs-increase the effectiveness of inhibitory synapses
- Removal of brain tissue
- In most cases, neuropsychological functioning improves after removal of brain regions
- Between seizures, large regions around irritated brain tissue are inhibited (seizure is when inhibition looses)
- When irritation is removed, it allows the other regions to function normally
What are the two types of stroke?
-Hemorrhagic stroke-caused by the rupture of a cerebral blood vessel
- Obstructive stroke-caused by occlusion of a blood vessel
- Ischemia-loss of blood flow to a region
- Thrombus-a blood clot that forms within a blood vessel which may occlude it
- Embolus-piece of matter that dislodges from its site or origin and occludes an artery
- Could be a blood clot, fat or bacterial debris
Describe the effects of damage caused by a stroke.
- Can vary from negligible to massive
- Damage is caused by an exitotoxic lesion
- When blood supply is interrupted, oxygen and glucose are quickly depleted.
- -This causes Na+/K+ pumps to stop
- -Nevers become depolarized due to slow leak of Na+ and release glutamate which cause neurons to become more depolarized and release more glutamate
- -Activation of NMDA receptors increases inflow of Na+ and Ca2+ ions
- -Excessive Na+ and Ca2+ is toxic to cells
- -High intracellular Na+ levels cause the cell to absorb water and swell
- -This causes microglia to become phagocytic
- -White blood cells are attracted which obstruct capillaries
- -Damaged mitochondria produce free radicals that destroy nucleic acids, proteins, and fatty acids
What is one common cause of “mental retardation”?
Toxin exposure during fetal development
What are the effects of prenatal exposure to nicotine?
- Increased likelihood of spontaneous abortion, fetal mortality, and SIDS
- deficits in synaptic connectivity and neurochemical activity
- Long term effects- behavioral problems:
- -Decreased IQ scores
- -ADHD
- -Conduct disorder
- -Deficits in problem solving skills and ability to cope with stress
Effects of prenatal exposure to alcohol
- Babies born to alcoholic women are smaller and develop slower
- Many have fetal alcohol syndrome
- Alcohol interferes with a neural adhesion protein that helps guide growth of neurons
- A safe level of alcohol has not been determined, though small amounts unlikely to cause harm
Phenylketonuria (PKU)
- Inherited lack of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine
- Excessive phenylalanine interferes with myelinization of neurons in the CNS
- Results in severe mental retardation with an IQ of approximately 20 by 6 years old
- Infant needs to be put on low phenylalanine diet
Down Syndrome
Delayed development
• Slow to learn to talk, though most talk by age 5
Brian changes
• Brian ~10% lighter
• Gyri and sulci are simpler and smaller
• Frontal lobe is small and superior temporal gyrus is thin
• After age 30, neural degeneration similar to Alzheimer’s
Tay-Sachs disease
- Heritable (mainly Eastern European Jewish descent), fatal, metabolic strorage disorder
- Lack of enzymes in lysosomes causes accumulation of waste produces and swelling of cells in brain
Pyridoxine dependency
- Results in damage to cerebral white matter, thalamus, and cerebellum
- Treated by large doses of vitamin B6
Galactosemia
- Inability to metabolize galactose (sugar in milk)
- Can cause damage to cerebral white matter and cerebellum
