Degenerative
Neurologic
Disorders
What is Degenerative Disorder?
Degenerative disorder is the result
of a continuous process based on
degenerative cell changes, affecting
tissues
or
organs,
which
will
increasingly deteriorate over time,
whether due to normal bodily wear or
lifestyle choices such as exercise or
eating habits.
Definition:
is a slowly progressive disease of the brain that is
characterized by impairment of memory and
eventually by disturbances in reasoning, planning,
language, & perception”
Etiology:
❑
❑
Idiopathic
Cholinergic hypothesis
▪ Caused by reduced synthesis of acetylcholine
❑
Amyloid hypothesis
▪ Abnormal breakdown; buildup of amyloid beta deposits
❑ Genetics
▪ Apolipoprotein E (APOE) is a gene that’s been linked to the
onset of Alzheimer’s symptoms in older adults.
SYMPTOMS
COGNITIVE
Memory loss
Aphasia
Apraxia
Agnosia
Disorientation
Impaired execution
function
NON-COGNITIVE
Depression, psychotic
symptoms
( Hallucination,
delusions)
Behavioural
disturbances
( Physical & verbal
aggression,
motor hyperactivity,
uncooperativeness)
FUNCTIONAL
Inability to care for self
• Memory loss that disrupts daily life.
• Challenges in planning or solving problems.
• Some people may experience changes in their ability to
develop and follow a plan or work with numbers. They may
have trouble following a familiar recipe or keeping track of
monthly bills.
• They may have difficulty concentrating and take much
longer to do things than they did before.
• Difficulty completing familiar tasks at home, at work.
• Confusion with time or place.
• Trouble understanding visual images and spatial relationships.
• New problems with words in speaking or writing.
• Misplacing things and losing the ability to retrace steps
• Decreased or poor judgment.
• Withdrawal from work or social activities.
• Changes in mood and personality
Diagnostic evaluation
History
Physical examination
(MSE) Mental State Examination
(used to evaluate the cognitive
impairments)
C.T Scan
MRI
PET
TREATMENT FOR COGNITIVE SYMPTOMS IN AD
MILD-MODERATE DISEASE:
Cholinesterase Inhibitor:
DONEPEZIL
RIVASTIGMINE
GALANTAMINE
MODERATE-SEVERE DISEASE:
Anti-glutamatergic drug:
MEMANTINE
CHOLINESTERASE INHIBITORS
1st line therapy for the symptomatic treatment of cognitive symptoms in mildmoderate AD.
TACRINE:
•
•
•
•
1St cholinesterase inhibitor approved for the treatment of Alzheimer’s
disease.
It was the 1st centrally acting anti-ChE.
It inhibits both AChE and BuChE.
Used to treat mild-moderateAD.
• Now, used rarely because of hepatotoxicity.
Alternative Medicine
• Omega-3 fatty acids. Omega-3 fatty acids in
fish may
help prevent cognitive decline.
Studies done on fish oil supplements haven't
shown any benefit, however.
• Curcumin. This herb comes from turmeric and
has antiinflammatory and antioxidant
properties that might affect
chemical
processes in the brain. So far, clinical trials
have found no benefit for treating Alzheimer's
disease.
• Vitamin E. Although vitamin E isn't
effective for preventing
Alzheimer's,
taking 2,000 international units daily may
help delay the progression in people who
already have the disease. However,
study results have been mixed, with only
some showing this benefit. Further
research into
the safety of 2,000
international units daily of Vitamin E in a
dementia population will be needed
before it can be routinely recommended.
Other Alzheimer’s treatments
In addition to medication, lifestyle changes may
help you manage your condition. For example, your
doctor might develop strategies to help you or your
loved one:
•focus on tasks
•limit confusion
•avoid confrontation
•get enough rest every day
•stay calm
Overview
Parkinson's disease is a progressive
nervous system disorder that affects
movement. Symptoms start gradually,
sometimes starting with a barely
noticeable tremor in just one hand.
Tremors are common, but the disorder
also commonly causes stiffness or
slowing of movement.
Parkinson’s Disease-Clinical features:
The classical syndrome:
Tremors
Rigidity
Bradykinesia
Loss of postural reflexes or instability
These may be absent initially, when non-specific
symptoms of tiredness, aching limbs, mental slowness,
depression & small handwriting (micrographia) may be
noticed.
Non-motor symptoms: anxiety, depression, sleep
disturbances, dementia
PATHOPHYSIOLOGY
The substantia nigra is a
region in the midbrain
that is considered part of
the basal ganglia. It looks
like a darkened streak in
unstained brain tissue;
this is where it gets its
name, which is Latin for
"black substance."
Dopamine is
responsible for
accuracy of
movement.
PARKINSON’S DISEASE
DOPAMINE
Movement
Disorders
Acetylcholine: excitatory neurotransmitter
Dopamine: inhibitory neurotransmitter
Acetylcholine
Dopamine
Dysfunction in the
Extrapyramidal System
Diagnostic tests
The diagnosis is made clinically, as there is
no diagnostic test for Parkinson's disease.
Imaging (CT or MRI) of the head may be
needed if there are any features
suggestive of pyramidal, cerebellar or
autonomic involvement, or the
diagnosis is otherwise in doubt (e.g to
exclude stroke).
Treatment
Parkinson's disease can't be cured, but medications
can help control the symptoms, often dramatically. In
some more advanced cases, surgery may be advised.
CURRENT PHARMACOLOGICAL THERAPIES
L-dopa (Levodopa)
Levodopa, the most effective
Parkinson's disease medication,
is a natural chemical that passes
into your brain and is converted
to dopamine.
Anticholinergic
therapy
Muscarinic receptor
antagonists; These have
a useful effect on tremor
& rigidity, but do not
help bradykinesia.
CURRENT PHARMACOLOGICAL THERAPIES
MAOB inhibitors
Selegiline and Rasagiline
belong to a class of drugs
called monoamine oxidase
inhibitors (MAOIs). They
slow the breakdown of
dopamine in the brain.
They have a fairly mild
anti-Parkinsonian effect in
their own right.
Amantadine
While the mechanism of
action of amantadine in
the treatment of PD is
not known, it is believed
to release brain
dopamine from nerve
endings making it more
available to activate
dopaminergic receptors.
Surgical procedures
Deep brain stimulation
-surgeons implant electrodes into a specific
part of your brain. The electrodes are
connected to a generator implanted in the
chest near the collarbone that sends electrical
pulses to your brain and may reduce your
Parkinson's disease symptoms.
Stereotactic thalamotomy
-works by destroying part of
the thalamus to block the
abnormal brain activity from
reaching the muscles and
causing tremor.
• Physiotherapy& rehab:
• Patients at all stages of Parkinson's
disease benefit from physiotherapy,
which helps reduce rigidity&
corrects abnormal posture.
• Speech therapy may help in cases
where dysarthria & dysphonia
interfere with communication.
Huntington’s
Disease
Huntington’s Disease
Huntington's disease is an Neurodegenerative disorder
that causes the progressive breakdown of nerve cells in
the brain especially damage in BASAL GANGLIA
Huntington's disease has a broad impact on a
person's functional abilities and usually results in
movement, thinking (cognitive) and psychiatric
disorders.
Most people with Huntington's disease develop signs
and symptoms in their 30s or 40s, but the onset of
disease may be earlier or later in life.
When disease onset begins before age 20, the
condition is called juvenile Huntington's disease.
Huntington's disease usually causes
movement,
cognitive and
psychiatric disorders with a wide spectrum of signs and
symptoms.
Which symptoms appear first varies greatly among affected
people. During the course of the disease, some disorders
appear to be more dominant or have a greater effect on
functional ability.
Movement disorders
The movement disorders associated with Huntington's disease
can include both involuntary movements and
impairments in voluntary movements:
Involuntary jerking or writhing movements (chorea)
Muscle problems, such as rigidity or muscle contracture
(dystonia)
Slow or abnormal eye movements
Impaired gait, posture and balance
Difficulty with the physical production of speech or
swallowing
Cognitive disorders
Cognitive impairments often associated with
Huntington's disease include:
Difficulty in focusing on tasks
Lack of flexibility or the tendency to get stuck on a
thought, behavior or action (perseveration)
Lack of awareness of one's own behaviors and abilities
Slowness in processing thoughts or ''finding'' words
Difficulty in learning new information
Psychiatric disorders
The most common psychiatric disorder associated with
Huntington's disease is depression. Depression appears to
occur because of injury to the brain and subsequent changes
in brain function. Signs and symptoms may include:
Feelings of irritability, sadness
Social withdrawal
Insomnia
Fatigue and loss of energy
Frequent thoughts of death, dying or suicide
Causes
Huntington's disease is caused by an inherited defect in a single
gene. Huntington's disease is an autosomal dominant
disorder, which means that a person needs only one copy of the
defective gene to develop the disorder.
With the exception of genes on the sex chromosomes, a person
inherits two copies of every gene — one copy from each parent. A
parent with a defective Huntington gene could pass along the
defective copy of the gene or the healthy copy. Each child in the
family, therefore, has a 50 percent chance of inheriting the gene
that causes the genetic disorder.
Complications
The clinical depression associated with Huntington's
disease may increase the risk of suicide.
▪ Lack of physical activity, dietary problems, and eating and
swallowing problems can cause constipation, incontinence,
and weight loss
▪ Psychiatric and cognitive problems can lead to social
isolation and deep depression
The patient is usually bedridden in the final stages.
Common causes of death include:
Pneumonia or other infections
Injuries related to falls
Complications related to the inability to swallow
Tests and diagnosis
A diagnosis of Huntington's disease is based on
1) general physical exam
2) a review of your family medical history
3) neurological and psychiatric examinations.
Neurological examination
Motor symptoms
Reflexes
Muscle strength
Muscle tone
Coordination
Balance
Sensory symptoms
Sense of touch
Vision and eye movement
Hearing
Psychiatric symptoms
Mental status
Mood
Neuropsychological testing
The neurologist may also perform
standardized tests to assess:
Memory
Reasoning
Mental ability
Language function
Spatial reasoning
Brain imaging and function
Brain-imaging tests is used for assessing the structure or function of the
brain. The imaging technologies may include MRI, which can produce
detailed cross-sectional and 3-D images of the brain, or CT scan, which
produces cross-sectional images.
These images may reveal structural changes at particular sites in the
brain affected by Huntington's disease, although these changes may not
be apparent early in the course of the disease.
Treatments
▪ No treatments can alter the course of Huntington's disease.
▪ Collaborative goals focus on:
▪ - Reducing symptoms
▪ - Preventing complications
▪ - Providing support and assistance to the patient and
significant others
drugs to treat some symptoms may result in side effects
that worsen other symptoms.
MEDICATIONS
Medications for movement disorders
Drugs to treat movement disorders include the following:
Tetrabenazine (Xenazine) is used to suppress the
involuntary jerking and writhing movements (chorea)
associated with Huntington's disease.
Antipsychotic drugs, such as haloperidol (Haldol) and
chlorpromazine, have a effect of suppressing movements
(treat’s chorea)
Other medications that may help suppress chorea include
amantadine, levetiracetam (Keppra) and clonazepam (Klonopin).
Psychotherapy
A psychotherapist — a psychiatrist, psychologist or clinical social
worker — can provide talk therapy to help a person manage behavioral
problems, develop coping strategies, manage expectations during
progression of the disease and facilitate effective communication
among family members.
Occupational therapy
Handrails at home
Assistive devices for activities such as bathing and dressing
Eating and drinking utensils adapted for people with limited fine
motor skills
Speech therapy
Huntington's disease can significantly impair control of
muscles of the mouth and throat that are essential for
speech, eating and swallowing. A speech therapist can
help improve your ability to speak clearly or teach you to
use communication devices — such as a board covered
with pictures of everyday items and activities. Speech
therapists can also address difficulties with muscles used
in eating and swallowing.
Factors regarding eating and nutrition include the
following:
People with Huntington's disease often have
difficulty maintaining a healthy body weight. To get
adequate nutrition, more than three meals a day may be
necessary.
Difficulty with chewing, swallowing and fine motor
skills can limit the amount of food you eat and
increase the risk of choking.
Eventually, a person with Huntington's disease will need
assistance with eating and drinking.
AMYOTROPHIC
LATERAL SCLEROSIS
(ALS)
What is ALS?
• Progressive neurodegenerative disease in which the motor neurons
gradually degenerates and after some time, they eventually die.
• ALS is often called Lou Gehrig's disease, after the baseball player who
was diagnosed with it. Doctors usually don't know why ALS occurs. Some
cases are inherited.
• ALS often begins with muscle twitching and weakness in a limb, or
slurred speech. Eventually, ALS affects control of the muscles needed to
move, speak, eat and breathe. There is no cure for this fatal disease.
MOTOR NEURO
Motor neuron is a type of
nerve that can be found in
the spinal cord, brain, and
brain stem. It provides a
connection between
voluntary muscle of the
body and nervous system
Causes
In ALS, MN get affected and so messages
cannot be initiated or transferred to the
muscles, this means movement will not
be supported in the muscles leads to
weakness of the muscles and they also
get thinner.
-As the condition reaches its later stages,
more and more MN are damaged and
more voluntary muscles fail to function
then a person will be unable to move
their limbs and body eventually leads to
complete paralysis
Movement will not be
supported
No action
potential
Muscle weakens and
becomes thinner, inability to
control movement
Motor neurons
get affected
Summary of pathophysiology
Glutamate
Calcium
influx
Degradation
of neurons
No action
potential
transmitted
Denervation of
motor neurons
Death of
neurons
Clinical manifestations
Early stage
• Dysphagia
• Dysarthria
• Emotional lability
• Spasticity
• Fasciculation's
• Cramps
• Muscle weakness
• Atrophy
Progression
• Dyspnea
• Loose the ability to walk, or use
hands and arms
• Loose the ability to speak, and
swallow
Late stage
• Dementia
•Respiratory failure
•Aspiration pneumonia
•Occulomotor nerve of extra ocular muscle
is affected
•May resemble locked in syndrome
TREATMENT
•NO curative agent
•RILUZOLE- the only drug approved by the
FDA
• Riluzole is in a class of medications called
benzothiazoles. It works by changing the activity
of certain natural substances in the body that
affect nerves and muscles.
THERAPY
• Physical Therapy
-involves exercises
• Speech Therapy
-text -to-speech applications
Maintenance
-get regular check ups
-nutritional counseling