Neurological Diseases
Epilepsy
Parkinsonism
Epilepsy
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Seizures that occur on a chronic, recurrent
basis
Thought to be caused by damage to the
network of cortical neurons that have
become capable of sustaining an excessive
discharge pattern for several seconds
The results of this excessive discharge
pattern is a seizure
Question

If the damage to the cortical neurons is
permanent, why don’t seizures occur
all the time?
Answer
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There is an interplay between environmental and
internal brain factors
The normal neuronal control mechanisms that
contain and control abnormal neuronal firing are
overcome
Sometimes fatigue and sleep loss can trigger a
seizure
Normally impossible to determine what sets off
seizures in most patients with epilepsy
Non-Epilepsy Seizures
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Isolated seizures caused by a number of potentially
reversible problems
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CNS trauma, infection, or stroke
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Blunt force trauma to the brain, concussions, damage to parts of
brain, patients who had strokes
Hyponatremia and hypoglycemia
Hypoxia
Alcohol withdrawal
Fever (mainly in children)
If underlying causes of seizures are not corrected,
may lead to the development of recurrent seizures
or epilepsy
Etiology
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The cause of 80% of the seizures in
patients with epilepsy are unknown
The most common causes of epilepsy
include head trauma and stroke
CNS tumors and infections are also
common causes
Epidemiology
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2 million in US are afflicted
Incidence is between 35-75 cases/100,000
persons
About 8% of population will experience a
seizure during their lifetime
New onset seizures occurs most frequently
in infants <1 month of age and in adults >55
years old

More chances in very young and very old
Classification of Seizures
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Partial seizures
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Simple partial seizures
Complex partial seizures
Secondary generalized
Generalized seizures
Simple Partial Seizures
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Caused by a group of hyperactive neurons
confined to a single locus in brain
Patient experiences abnormal sensations or
uncontrolled muscle movements in a portion
of their body
Patient does not lose consciousness
Complex Partial Seizures
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Also caused by a group of hyperactive
neurons confined to a single locus in brain
Patient may experience sensory
hallucinations and mental distortions
Abnormal muscle movements may include
chewing movements and loss of bowel or
urine control
Patient may lose consciousness
Secondary Generalized
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Generalized seizures that begin as
simple or complex partial seizure and
spread to involve the entire brain
Many patients complain of a “aura”
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Aura may be the beginning of the seizure
Generalized Seizures
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Entire cortex is involved from the onset
of the seizure
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Tonic-clonic seizures
Absence seizures
Myoclonic seizures
Atonic seizures
Tonic-Clonic Seizures
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Sudden loss of consciousness
accompanied by tonic extension and
rhythmic clonic contractions of all
major muscle groups.
The duration of the seizure is usually 1
to 3 minutes.
This type of seizures are often called
grand mal
Absence Seizures
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Sudden and brief loss of
consciousness without muscle
movements.
These seizures are often described as
daydreaming or blanking out episodes
Seizures often called petit mal
Myoclonic Seizures
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Single and very brief jerks of all major
muscle groups lasting 3-4 seconds
Patients with these may not lose
consciousness
Patients describe seizures as shoulder
shrugs or spinal chills.
May cluster and build into a generalized
tonic-clonic seizures.
Atonic Seizures
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The patient loses consciousness and
muscle tone.
No muscle movements are typically
noted
Patient falls if not sitting or lying down
Often described as “falling out”
Overview of Treatment
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Selecting appropriate therapy is dependent upon
identifying and understanding the different seizure types
Selecting appropriate therapy is dependent mechanism
of action, effectiveness, adverse effects, and potential
for drug interactions
Doses must be individualized using titration to minimize
adverse effects and maximize therapeutic benefits
Selecting appropriate therapy is based upon some
knowledge, experience, luck and “black magic”
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In many cases, no logical approach
“black magic?” – wagner calls it this because in some cases there is
no logical approach to tx or seizures
Mechanisms of Action
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Glutamate is the major excitatory neurotransmitter in
the cerebral cortex
Glutamate is released from presynaptic neurons and
attaches to cetain receptor sites on postsynaptic
neurons.
This results in a opening of membrane channels
allowing calcium or sodium to flow into the
postsynaptic neurons thus depolarizing it and
transmitting an excitatory signal
Phenytoin, carbamazepine, and lamotrigine interfere
with this mechanism (interfere w/stimulatory mech)
Mechanisms of Action
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GABA is the major inhibitory neurotransmitter in the
cerebral cortex
GABA attaches to neuronal membranes and opens
chloride channels
When chloride flows into the neuron, it becomes
less excitable.
Mechanism causes seizure activity to be “shut off”
by controlling excessive neuronal firing.
Benzodiazepines work by enhancing action of
GABA
Approach to Treatment
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Type of seizures must be determined
Determine if there is an underlying cause
Risk of subsequent should be determined
If it is determined that the patient has “real”
seizures and if there is a risk of subsequent
seizures, drugs are given
Approach to Treatment
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In the design of pharmacological plan,
the patient
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Must be willing to take the medication
Must be willing to monitor seizure
frequency
Most be willing to monitor adverse
reactions
Selection of Treatment
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Proper identification of seizure type is
helpful in selecting appropriate therapy
Adverse reaction patterns and economic
factors should be considered
Follow consensus recommendations for
treatment by American Academy of
Neurology
Effectiveness of Treatment
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50% of patients with epilepsy can be
completely controlled
Of the remaining 50%
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25% have meaningful improvement with
treatment
25% of patients do not respond well
Generic Name
Brand
Name
Dose related Side Effects
Idiosyncratic
Side Effects
Divalproex sodium
Depakote
Drowsiness, nausea, tremor
Hepatotoxicity
Lamotrigine
Lamaictal
Drowsiness, headache
Rash
Levetiracetam
Keppra
Drowsiness, dizziness
Depression
Phenytoin
Dilantin
Drowsiness, diplopia, ataxia
Rash, others
Topiramate
Topamax
Drowsiness, ataxia, dizziness
acute myopia
and glaucoma
Carbamazepine
Tegretol
Drowsiness, nausea, diplopia
Aplastic anemia
Oxycarbazepine
Trileptal
Drowsiness, diplopia
Hyponatremia
Gabapentin
Neurontin
Drowsiness
Edema
Pregabalin
Lyrica
Drowsiness, ataxia, diplopia
Edema
General Consultation
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Take medication with a glass of water.
Follow the directions on the prescription label. Take your doses at
regular intervals about the same time every day
Do not take your medicine more often than directed.
If you miss a dose, take it as soon as you can. If it is almost time for
your next dose, take only that dose. Do not take double or extra
doses.
Visit your doctor or health care professional for a regular check on
your progress.
Do not change brands or dosage forms of this medicine without
discussing the change with your doctor
If you are taking this medicine for epilepsy do not stop taking it
suddenly
Consultation
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You should keep a record at home of how
you feel and how your condition is
responding to treatment
You should share this information with your
doctor or health care professional at each
visit.
You should contact your doctor or health
care professional if your seizures get worse
or if you have any new types of seizures
Many Problems
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Many, many adverse effects
Adverse frequently cause drug to be
discontinued
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Dose related
Idiosyncratic
Many drug interactions
Generic Name
Brand
Name
Dose related Side Effects
Idiosyncratic
Side Effects
Divalproex sodium
Depakote
Drowsiness, nausea, tremor
Hepatotoxicity
Lamotrigine
Lamictal
Drowsiness, headache
Rash
Levetiracetam
Keppra
Drowsiness, dizziness
Depression
Phenytoin
Dilantin
Drowsiness, diplopia, ataxia
Rash, others
Topiramate
Topamax
Drowsiness, ataxia, dizziness
acute myopia
and glaucoma
Carbamazepine
Tegretol
Drowsiness, nausea, diplopia
Aplastic anemia
Oxcarbazepine
Trileptal
Drowsiness, diplopia
Hyponatremia
Gabapentin
Neurontin
Drowsiness
Edema
Pregabalin
Lyrica
Drowsiness, ataxia, diplopia
Edema
Idiosyncratic Side Effects
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Rash including Stevens-Johnson
Syndrome
Hepatotoxicity
Bone marrow toxicity
These side effects are potentially lifethreatening
Drugs Associated with most
Idiosyncratic Reactions
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Carbamezepine
Phenytoin
Valproate
Lamotrigine
Parkinson’s Disease (PD)
Overview
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Patients display motor and non-motor
symptoms
The most useful diagnostic tool is the clinical
history
Therapy is begun when the disease affects
quality of life
Disease is progressive
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Late stages of the disease may be associated
with dementia
Epidemiology
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Affects 1 million Americans
Average age of onset is >60 years old
Genetics may play a role in that 15%
of patients with PD have a first-degree
relative with the disease
Etiology
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Cause is unknown
Deterioration and eventual death of
nerve cells in the substantia nigra
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Neurotransmitters needed for normal fx
are reduced
Motor Symptoms – “TRAP”
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T = Tremor at rest ("pill rolling")
R = Rigidity
A = Akinesia or bradykinesia
P = Postural instability and gate
abnormalities
Non-Motor Symptoms –
“SOAP”
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S = Sleep disturbances insomnia, rapid eye movement sleep
behavioral disorder, restless legs syndrome
0 = Other miscellaneous symptoms nausea
fatigue, speech, pain, dysesthesias, vision, seborrhea
A = Autonomic symptoms drooling, constipation, sexual
dysfunction, urinary problems, sweating, orthostatic
hypotension, dysphagia
P = Psychological symptoms anxiety, psychosis, cognitive
impairment, depression
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Psychological impairment Cognitive impairment, depression,
dimensia
Response Fluctuations - MAD
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M= Motor fluctuations
A = Akathisia
D = Dyskinesias
Approach to Treatment
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Three phases
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Lifestyle changes, nutrition, exercise
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Pharmacological treatment with drugs that enhance
dopamine concentrations
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Helps in early stages
Want to decrease progression of disease, but majority of the
time it’s not possible
Surgical treatment
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take pt, do NOT anesthetize  open up patient’s skull(do
use SOME anesthetic)  expose the brain(brain has no pain
receptors)
Take electrodes and put on parts of brain that theoretically is
controlling abnormal movements
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Apply electrical stimulation to those areas, if you hit electrical impulses,
everything stops
Classification of Drugs
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2 types of drugs for tx:
1.
2.
Drugs which increase dopamine
concentration or activity
Drugs which block acetylcholine
1.
Theoretically better, but in reality are A LOT
less effective, used as an adjunct (NOT as
primary tx)
Levodopa
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DOPA is metabolic precursor to dopamine
Restores dopamine levels in substantia
nigra
Levodopa must be converted to dopamine
in dopamanergic neurons
As disease progresses(more dopramanergic
neurons are destroyed in brain)  response
to L-Dopa declines less dopamanergic
neurons are present to convert DOPA to
dopamine
Results of Treatment with LDOPA
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Must use high doses
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Causes significant nausea and vomiting
Causes significant orthostatic hypotension (especially in
elderly)– most of time elderly has it)
With chronic treatment, patients often complain that
drug effects wears off resulting in development of
motor fluctuation
Relief provided by levodopa is only symptomatic
and temporary
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Does not halt progression of disease
Carbidopa
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Carbidopa is a dopa decarboxylase inhibitor
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Used in combination with levodopa
(Sinemet  combo of L-dopa and
carbidopa)
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Decreases metabolism of levodopa in GI tract
and peripheral tissues
Can use a lot less L-dopa
Increases available of levodopa in CNS
May decrease dose of levodopa five-fold
and thus decrease incidence of side effects
Consultation
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Take orally with water at least 30 minutes before
eating or 1 hour after meals to maximize absorption
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May be taken with a small non-protein snack, such as fruit
or a cracker, to avoid nausea.
Administering with food may decrease absorption.
***Causes orthostatic hypotension **Do not stand
or sit up quickly, especially if you are an older
patient. This reduces the risk of dizzy or fainting
spells
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Good advice for any pt that causes orthostatic
hypotension
Consultation
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Visit your doctor or health care professional for regular checks
on your progress.
It may be several months before you feel the full benefits of
this medicine.
Continue to take your medicine on a regular schedule
You may experience a wearing of effect of this medication
You may also experience an on-off effect where the medicine
apparently stops working
Tell your doctor or health care professional if any of these
symptoms happen to you. Your dose may need to be
changed.
Psychiatric disturbances
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Psychiatric disturbances can occur including
agitation, anxiety, confusion, dizziness, headache,
euphoria, insomnia, memory loss, nightmares, toxic
delirium, hallucinations, paranoid delusion,
psychosis, and hypomania and depression
Sinemet’s psychiatric effects tend to be progressive
and frequently a compromise must be reached
between psychiatric effects and control of parkinson
symptoms.
Dopamine Agonists
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Pramipexole
Mirapex
Ropinirole
Requip
Directly stimulate dopamine receptor
sites in brain
Actions similar to levodopa
Severe side effects limit usefulness
Consultation
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Take this medicine with a glass of water.
Take it with or without food but if it upsets
your stomach, take it with food.
Do not stop taking this medicine except on
your doctor's advice.
Do not stand or sit up quickly, especially if
you are an older patient. This reduces the
risk of dizzy or fainting spells. (orthostatic
hypotension)
Antimuscarinic Drugs
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Much less effective that other drugs
Used as an adjunct to
levodopa/carbidopa
Adverse effects similar to high doses
of atropine
Benztropine
Cogentin
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(on top 200)
Consultation
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May be administered without regard to meals
Your mouth may get dry. Chewing sugarless gum or sucking
hard candy, and drinking plenty of water may help
This medicine may cause dry eyes and blurred vision. If you
wear contact lenses you may feel some discomfort.
Lubricating drops may help.
You may sweat less than usual while you are taking this
medicine. As a result your body temperature could rise to a
dangerous level.
Be careful not to get overheated during exercise or in hot
weather. You could get heat stroke.
Avoid taking hot baths and using hot tubs and saunas.