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Disorders of the Nervous System (NEUROPATHOLOGY (Amyloid-β (Accumulates…
Disorders of the
Nervous System
ALZHEIMER’S DISEASE
a type of dementia that causes problems
with memory, thinking and behavior
Alzheimer's is the most common form of
dementia
Mild cognitive decline progresses to severe dementia and death in 3-10 years
PREVALENCE
Most common in the elderly
Currently ranked as the 6th leading cause of death
Prevalence is increasing
SYMPTOMS :explode:
Mild
May function independently
Memory lapses
Problems coming up with the right word or name
Trouble remembering names when introduced to new people
Challenges performing tasks in social or work settings.
Forgetting material that one has just read
Losing or misplacing a valuable object
Increasing trouble with planning or organizing
Moderate
Can be difficult to express thoughts and perform routine tasks
May express frustration or act in unexpected ways
Symptoms are noticeable to others
Symptoms are noticeable to others
Forgetfulness of events or about one's own personal history
Feeling moody or withdrawn, especially in socially or mentally challenging situations
Being unable to recall their own address or telephone number
or the high school or college from which they graduated
Confusion about where they are or what day it is
The need for help choosing proper clothing for the season or the occasion
Trouble controlling bladder and bowels in some individuals
Changes in sleep patterns, such as sleeping during the day
and becoming restless at night
An increased risk of wandering and becoming lost
Personality and behavioral changes, including suspiciousness
and delusions or compulsive, repetitive behavior like handwringing or tissue shredding
Severe
Lose ability to respond to environment, converse, and control movement
Need extensive help with daily activities
Symptoms include
Need round-the-clock assistance with daily activities and personal care
Lose awareness of recent experiences as well as of their surroundings
Experience changes in physical abilities, including the ability
to walk, sit and, eventually, swallow
Have increasing difficulty communicating
Become vulnerable to infections, especially pneumonia
NEUROPATHOLOGY
Amyloid-β
Accumulates inside and outside of neurons
(years before symptoms)
Damages dendritic spines, decreases synaptic input, decreases plasticity
Damaged dendrites and axons cluster into
plaques
Accumulating plaques cause atrophy in cortex, hippocampus
Tau protein
High levels of amyloid alter tau proteins, part of a neurons
intracellular support structure
Altered tau cannot bind to microtubules and they spread into
cell body and dendrites
Tau aggregates into neurofibrillary tangles
treatment
Current approaches focus on helping people maintain
mental function, manage behavioral symptoms, and slow
or delay the symptoms of disease
Cholinesterase inhibitors for mild to moderate AD
Increase acetylcholine levels, which the disease decreases
NMDA receptor antagonist
Excessive glutamate can lead to cell death
Can delay worsening mental abilities
Death of substantia nigra dopamine neurons：
Accumulates inside and outside of neurons (years before
symptoms)
Without dopamine input basal ganglia function is impaired
Increased inhibitory input to thalamus
Less input to guide motor actions
TREATMENTS
L-DOPA
Precursor in dopamine synthesis
Side effects –dyskinesia (unwanted movements),
impulse control disorders
Deep Brain Stimulation
Electrical stimulation to GPi or
subthalamic nucleus (indirect pathway)
DBS prevents target brain
region from sending
messages
PARKINSON’S DISEASE
Neurodegenerative brain disorder that progresses slowly in most people
Although the disease itself is not fatal, the complications
caused by Parkinson’s are the 14th leading cause of death
in the United States
The symptoms caused by Parkinson’s include an ongoing
loss of motor as well as a wide range of non-motor symptoms
Currently it is incurable
CAUSES
Some genetic risk, though no gene
alone increases risk greatly
Environmental – exposure to toxins like insecticides
Traumatic head injury
Genetic-environmental interactions lead to degeneration
Symptom :explode:
Tremor
: can occur at rest, in the hands, limbs, or can be postural
Muscular
:
stiff muscles
problems with coordination
Sleep
: early awakening, nightmares, restless sleep, or sleep disturbances
Whole body
:
fatigue, dizziness, poor balance, or restlessness
Cognitive
:
amnesia
, confusion in the evening hours,
dementia
,
or difficulty thinking and understanding
Speech
: impaired voice, soft speech, or voice box spasms
Mood
: anxiety or apathy
Nasal
: distorted sense of smell or loss of smell
Urinary
: dribbling of urine or leaking of urine
Facial
: jaw stiffness or reduced facial expression
EPILEPSY :explode:
Characterized by repeated episodes of excessive
synchronized neural activity, “seizure”
1 to 2 percent of people affected
Most epilepsy is well controlled
Can be caused by genetic anomaly (gene controlling
GABA receptor), trauma, infection, tumor, toxins
SEIZURE
A seizure is a sudden surge in electrical activity in the brain
Seizures can vary in intensity and symptoms
Can be a symptom of epilepsy or triggered by
stress
low blood sugar
heatstroke
alcohol withdrawal
medications
sleep deprivation
infection/fever
TYPES OF SEIZURES :explode:
Generalized onset seizures
Affect both sides of the brain at the same time
Tonic-clonic
Classic seizure, convulsion
Loss of consciousness
Muscles stiffen (tonic), jerking movements (clonic)
Absence
Stops all activity, blank look
Lasts < 10 sec
Atonic
Loss of muscle tone
Lasts < 15 sec
Focal onset seizures (most common type)
Begin in one area on one side of the brain
Aware seizures – patient is awake and aware
Impaired awareness seizures – patient confused or stares blankly
Automatisms – move mouth, pick clothing, etc.
Amnesia
Often originate in frontal or temporal lobe
Temporal lobe epilepsy
:explode:
Most common form of focal onset epilepsy
(60% of all people with epilepsy) (remember H.M.)
Auras occur (in aware seizures)
Déjà vu experiences
Fear, panic, anxiety
Sensory hallucinations
Memory loss is common
Geschwind syndrome
Deepened emotions, circumstantial thought, increasing concern with religious beliefs, change in sexual behavior, excessive writing
Describes some individuals with TLE but controversy over whether this is a true syndrome
TREATMENTS
Antiepileptic drugs
Block sodium flow across cell membrane
Enhance effects of GABA
Effective for 7 out of 10 cases
Surgery
Remove focus of seizure
This is the point where the seizure usually begins
Brain stimulation
Detects patterns that lead to seizure
Sends disruptive electrical signal to prevent onset
MULTIPLE SCLEROSIS
Autoimmune disorder that damages myelin
Axons that have lost myelin cannot conduct action potentials
Symptoms
include
Visual disturbances
Muscle weakness
Trouble with balance
Numbness
Thinking and memory problems :explode:
More prevalent in women, begins between 20 and 40 years
Can be mild or severe, losing ability to walk and talk
TREATMENTS
Is currently incurable
Treatments manage symptoms and slow progression
Anti-inflammatory
Corticosteroids
Interferon-beta (cytokine)
Immunosuppressant
HUNTINGTON'S DISEASE
An inherited condition in which nerve cells in the brain break down over time.
Symptom :explode:
Cognitive
:
amnesia, delusion, lack of concentration
, memory loss, mental confusion, slowness in activity, or difficulty thinking and understanding
Muscular:
abnormality
walking, increased muscle activity,
involuntary movements
,
problems with coordination
, loss of muscle, or muscle spasms
Behavioral:
compulsive behavior, fidgeting, irritability, or lack of restraint
Psychological:
delirium, depression, hallucination
, or paranoia
Mood
: anxiety, apathy, or mood swings